Identification Number:
DI 23022 TN 34
Intended Audience:See Transmittal Sheet
Originating Office:ORDP ODP
Title:Processing Quick Disability Determination (QDD) and Compassionate Allowance (CAL) in the Disability Determination Services (DDS)
Type:POMS Transmittals
Program:Title II (RSI),Title XVI (SSI),Disability
Link To Reference:
 

PROGRAM OPERATIONS MANUAL SYSTEM
Part DI – Disability Insurance
Chapter 230 – Special Issues
Subchapter 22 – Processing Quick Disability Determination (QDD) and Compassionate Allowance (CAL) in the Disability Determination Services (DDS)
Transmittal No. 34, 08/28/2020

Audience

PSC: CS, DEC, DTE, IES, RECONR;
OCO-OEIO: CR, ERE, FCR, FDE, RECONE;
OCO-ODO: DE, DEC, DS, RECONE;
ODD-DDS: ADJ, DHU;

Originating Component

ODP

Effective Date

08/28/2020

Background

This is a Quick Action Transmittal. These revisions do not change or introduce new policy or procedure.

Summary of Changes

DI 23022.095 Alexander Disease

  • Added "ICD-10-CM" to heading;

  • Added ICD-10 information to summary;

  • Added bulleted list for information in "Diagnostic testing" and "Suggested MER for Evaluation" sections;

  • Added bulleted list for "Physical findings" using information provided in the "Description" section;

  • Revised suggested listings for evaluation to be listed in numerical order

DI 23022.127 CACH - Vanishing White Matter Disease - Congenital, Infantile, and Early Childhood Onset Forms

  • Added "ICD-10-CM" to heading;

  • Added ICD-10 information to summary;

  • Revised abbreviation in "Description" for consistency;

  • Added bulleted list for "Physical findings" using information provided in the "Description" section;

  • Added definitions for various medical terms to be consistent with formatting of other impairment summaries;

  • Added "or" to suggested listings for evaluation under "Meets"

DI 23022.130 Canavan Disease

  • Added "ICD-10-CM" to heading;

  • Added ICD-10 information to summary;

  • Updated "Alternate Names" section;

  • Added bulleted list for "Physical findings" using information provided in the "Description" section;

  • Corrected listings information in "Suggested Listings for Evaluation"

DI 23022.141 Coffin-Lowry Syndrome

  • Added "ICD-10-CM" to heading;

  • Added ICD-10 information to summary;

  • Updated "Alternate Names" section;

  • Revised abbreviation in "Description" for consistency;

  • Added bulleted list for information in "Diagnostic testing" and "Physical findings" sections

DI 23022.143 Congenital Myotonic Dystrophy

  • Added "ICD-10-CM" to heading;

  • Added ICD-10 information to summary;

  • Updated "Alternate Names" section;

  • Combined first two sentences of "Description" section;

  • Added bulleted list for information in "Diagnostic testing" and "Physical findings" sections

DI 23022.145 Creutzfeldt-Jakob Disease (CJD)

  • Added "ICD-10-CM" to heading;

  • Added ICD-10 information to summary;

  • Updated spacing throughout summary; Added definitions for abbreviations in "Diagnostic testing" section

DI 23022.160 Farber's Disease

  • Added "ICD-10-CM" to heading;

  • Added ICD-10 information to summary;

  • Updated "Alternate Names" section;

  • Revised "Description" section for readability;

  • Added bulleted list for "Physical findings" using information provided in the "Description" section;

  • Added bulleted list for information in "Diagnostic testing" section

DI 23022.165 Friedreich's Ataxia (FRDA)

  • Added "ICD-10-CM" to heading;

  • Added ICD-10 information to summary;

  • Added bulleted list for "Physical findings" using information provided in the "Description" section

DI 23022.170 Frontotemporal Dementia (FTD), Pick's Disease -Type A

  • Added "ICD-10-CM" to heading;

  • Added ICD-10 information to summary;

  • Updated "Alternate Names" section;

  • Added bulleted list for "Physical findings" using information provided in the "Description" section

DI 23022.181 Giant Axonal Neuropathy

  • Updated "Alternate Names" section;

  • Added "ICD-10-CM" to heading;

  • Added ICD-10 information to summary;

  • Updated ICD-9 code information

DI 23022.190 Head and Neck Cancers

  • Revised condition name in "Description" section to be consistent with the rest of the summary;

  • Added "ICD-10-CM" to heading;

  • Added ICD-9 and ICD-10 information to summary;

  • Added bulleted list for "Physical findings"

DI 23022.191 Hoyeraal-Hreidarsson Syndrome

  • Added "ICD-10-CM" to heading;

  • Added ICD-9 and ICD-10 information to summary;

  • Updated bulleted list for "Physical findings" using information provided in the "Description" section

DI 23022.195 Infantile Neuroaxonal Dystrophy (INAD)

  • Updated "Alternate names";

  • Added "ICD-10-CM" to heading;

  • Added ICD-9 and ICD-10 information to summary;

  • Added bulleted list for "Physical findings" using information provided in the "Description" section

DI 23022.202 Joubert Syndrome

  • Updated "Alternate names";

  • Updated information provided in the "Description" section;

  • Added "ICD-10-CM" to heading;

  • Added ICD-10 information to summary;

  • Updated bulleted list for "Physical findings" using information provided in the "Description" section

DI 23022.207 Kleefstra Syndrome

  • Added "ICD-10-CM" to heading;

  • Added ICD-10 information to summary;

  • Updated bulleted list for "Physical findings" using information provided in the "Description" section

DI 23022.210 Krabbe Disease (KD) - Infantile

  • Added condition abbreviation to "Description" section;

  • Added "ICD-10-CM" to heading;

  • Added ICD-9 and ICD-10 information to summary;

  • Updated bulleted list for "Physical findings" using information provided in the "Description" section;

  • Added bulleted list in "Suggested MER for Evaluation" section

DI 23022.220 Lesch-Nyhan Syndrome (LNS)

  • Added "ICD-10-CM" to heading;

  • Added ICD-9 and ICD-10 information to summary;

  • Added bulleted listing for "Physical findings"

DI 23022.235 Metachromatic Leukodystrophy (MLD)

  • Added "ICD-10-CM" to heading;

  • Added ICD-9 and ICD-10 information to summary;

  • Added "Diagnostic testing" heading;

  • Added bulleted list for "Physical findings" using information provided in the "Description" section

DI 23022.250 Ornithine Transcarbamylase (OTC) Deficiency

  • Added "ICD-10-CM" to heading;

  • Added ICD-9 and ICD-10 information to summary;

  • Added bulleted list for "Physical findings" using information provided in the "Description" section

DI 23022.261 Pallister-Killian Syndrome

  • Added "ICD-10-CM" to heading;

  • Added ICD-10 information to summary;

  • Corrected misspelling of chromosome in "Diagnostic testing";

  • Updated bulleted list for "Physical findings" using information provided in the "Description" section

DI 23022.280 Pompe Disease - Infantile

  • Added "ICD-10-CM" to heading;

  • Added ICD-9 and ICD-10 information to summary;

  • Added bulleted list for "Physical findings";

  • Revised suggested listings for evaluation to be listed in numerical order;

  • Revised spelling of condition throughout summary for consistency;

  • Revised spelling of "these" to "this" in Notes for "Suggested Listings for Evaluation"

DI 23022.281 Progressive Bulbar Palsy

  • Added "ICD-10-CM" to heading;

  • Added ICD-10 information to summary

DI 23022.285 Rett (RTT) Syndrome

  • Updated formatting of entire table to be consistent with all CAL impairment summaries;

  • Added "ICD-10-CM" to heading;

  • Added ICD-9 and ICD-10 information to summary;

  • Added bulleted list for "Physical findings"

DI 23022.296 Seckel Syndrome

  • Updated formatting of entire table to be consistent with all CAL impairment summaries;

  • Updated "Alternate names";

  • Added "ICD-10-CM" to heading;

  • Added ICD-10 information to summary;

  • Updated bulleted list for "Physical findings" using information provided in the "Description" section

DI 23022.297 Sjogren-Larsson Syndrome

  • Updated formatting of entire table to be consistent with all CAL impairment summaries;

  • Added "ICD-10-CM" to heading;

  • Added bulleted list for "Physical findings" using information provided in the "Description" section;

  • Added ICD-10 information to summary

DI 23022.300 Small Cell Cancer of the Large Intestine

  • Updated formatting of entire table to be consistent with all CAL impairment summaries;

  • Added "ICD-9-C/ICD-10-CM" to heading;

  • Added ICD-9 and ICD-10 information to summary;

  • Added bulleted list for "Physical findings" using information provided in the "Description" section

DI 23022.095 Alexander Disease

COMPASSIONATE ALLOWANCE INFORMATION
ALEXANDER DISEASE (ALX) - Neonatal and Infantile

ALTERNATE NAMES

Alexander Syndrome; Dysmyelogenic Leukodystrophy; Dysmyelogenic Leukodystrophy-Megalobar; Fribrinoid Degeneration of Astrocytes-Infantile type; Fibrinoid Leukodystrophy-Infantile type; Hyaline Panneuropathy; Leukodystrophy with Rosenthal Fibers; Megalencephaly with Hyaline Inclusion; Megalencephaly with Hyaline Panneuropathy

DESCRIPTION

Alexander disease (ALX) is one of a group of neurological conditions known as the leukodystrophies, disorders that are the result of abnormalities in myelin, the “white matter” that protects nerve fibers in the brain. ALX is a progressive and usually fatal disease. The destruction of white matter is accompanied by the formation of Rosenthal fibers, which are abnormal clumps of protein that accumulate in non-neuronal cells of the brain called astrocytes. Rosenthal fibers are sometimes found in other disorders, but not in the same amount or area of the brain that are featured in ALX.

Infantile form is the most common type of ALX. It has an onset during the first two years of life. Usually there are both mental and physical developmental delays, followed by the loss of developmental milestones, an abnormal increase in head size, and seizures. The disease occurs in both males and females, and there are no ethnic, racial, geographic, or cultural/economic differences in its distribution.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: A diagnosis of Alexander disease is usually based on:

  • Radiologic studies including MRI, CT scan, or ultrasound;

  • Genetic testing showing mutations in the GFAP gene;

  • Chorionic villus sampling (CVS) or amniocentesis; and

  • Brain biopsy or autopsy may be indicated in select cases if the diagnosis cannot be made through other means.

Physical findings:

  • Mental and physical developmental delays;

  • Loss of developmental milestones;

  • Abnormal increase in head size; and

  • Seizures.

ICD-9: 330.0

ICD-10: E75.25
PROGRESSION

The prognosis for ALX is generally poor. Most children with the infantile form do not survive past the age of 6.

TREATMENT

There is no cure for ALX, nor is there a standard course of treatment. Treatment of ALX is symptomatic and supportive, primarily consisting of attention to general care and nutritional needs, antibiotic therapy for infections, and management of associated complications such as anti-epileptic drug therapy for seizures. Surgical interventions, including placement of a feeding tube and/or shunting for hydrocephalus, may also be required.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

  • Clinical history and examination that describes diagnostic features of the impairment;

  • Detailed, current pediatric and neurological examination;

  • Routine laboratory tests; and

  • MRI findings may be characteristic of ALX.

Suggested Listings of Evaluation:
DETERMINATION

LISTING

REMARKS

Meets

110.08 B

ALX (neonatal) with confirmed molecular genetic testing.

111.17

Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.127 CACH - Vanishing White Matter Disease - Congenital, Infantile, and Early Childhood Onset Forms

COMPASSIONATE ALLOWANCE INFORMATION
CACH - VANISHING WHITE MATTER DISEASE - CONGENITAL, INFANTILE, AND EARLY CHILDHOOD ONSET FORMS

ALTERNATE NAMES

Childhood Ataxia with Central Hypomyelination; Childhood ataxia with diffuse central nervous system hypomyelination; CACH Syndrome; Leukoencephalopathy with Vanishing White Matter Disease; Leukoencephalopathy with Vanishing White Matter Myelinosis Centralis Diffusa; Cree Leukoencephalopathy; Cree Leukodystrophy

DESCRIPTION

Childhood Ataxia with Central Nervous System Hypomyelination/Vanishing White Matter Disease (CACH-VWM) is a progressive disorder that mainly affects the brain and spinal cord (central nervous system). This leukodystrophy disorder causes deterioration of the CNS white matter, which consists of nerve fibers covered by myelin. Myelin is the fatty substance that insulates and protects nerves. In most cases, children with CACH-VWM show no signs or symptoms of the disorder at birth. Affected children may have slightly delayed development of motor skills such as crawling or walking. During early childhood, previously healthy children begin to develop motor impairments, including abnormal muscle stiffness (spasticity) and difficulty with coordinating movements (ataxia). There may also be some deterioration of mental functioning, but this is not usually as pronounced as the motor impairments. Specific changes in the brain are seen using magnetic resonance imaging (MRI) are characteristic of CACH-VWM and may be visible before the onset of symptoms.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing : The diagnosis of CACH-VWM is made by:

  • Physical examination;

  • MRI demonstrating bilateral cerebral destruction of white matter; and

  • Genetic testing documenting mutations in one of the five causative gene mutations (EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5).

Physical findings: Affected children with CACH-VWM may have:

  • Slightly delayed development of motor skills such as crawling or walking;

  • Cerebellar ataxia (inability to coordinate balance, gait, extremity and eye movements);

  • Hypotonia (decreased muscle tone);

  • Spasticity (muscle stiffness or tightness);

  • Difficulty swallowing (bulbar symptoms);

  • Optic atrophy; and

  • Lethargy (lack of energy and enthusiasm).

ICD-9: 330.0

ICD-10: E75.25

PROGRESSION

With CACH-VWM, generally the earlier onset of symptoms and signs correlates with faster progression and worse prognosis. In congenital or antenatal form, onset is in utero and newborns present with hypotonia, feeding difficulties, and microcephaly; progression is rapid with systemic involvement, development of intractable seizures, coma, and death before age 1. The infantile form has onset in the first months of life, similar rapid progression, motor dysfunction, and death usually by age 2 years. The early childhood onset form is the most common with onset between 1 and 5 years, with less spasticity and usually no cognitive decline. Most children with the early childhood form die within a few years of onset. In older children, adolescents, and adults, the clinical course is usually more slowly progressive than earlier onset forms, with spastic diplegia and ataxia, relative sparing of cognition, and typically longer survival.

TREATMENT

Currently there is no cure for CACH-VWM disease. Treatment is symptom specific and supportive. Physical therapy and rehabilitation may be prescribed for motor dysfunction (e.g. spasticity and ataxia); antiepileptic drugs for seizures. Referral to age-appropriate early childhood intervention program or special education.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

  • Clinical history and examination that describes the diagnostic features of the impairment;

  • Imaging studies; and

  • Genetic testing revealing a mutation in the EIF2B gene is definitive.

Suggested Listings for Evaluation:

DETERMINATION

LISTING REMARKS
Meets 110.08 A or B

111.17

Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.130 Canavan Disease

COMPASSIONATE ALLOWANCE INFORMATION

CANAVAN DISEASE (CD)

ALTERNATE NAMES

Aminoacylase-2 (ACY2) deficiency; Aspartoacylase (ASPA) deficiency; Canavan's leukodystrophy; Spongy Degeneration of the Central Nervous System or Neuroaxis; Van Bogaert-Bertrand syndrome; ACY2 deficiency; Canavan's disease; ASPA deficiency

DESCRIPTION

Canavan disease (CD) is a severe progressive inherited (genetic) disorder of the central nervous system (CNS). It is one of the most common cerebral degenerative diseases of infancy, is a gene-linked, neurological birth disorder in which the white matter of the brain degenerates into spongy tissue riddled with microscopic fluid-filled spaces. CD is one of a group of genetic disorders known as the leukodystrophies. These diseases cause imperfect growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers in the brain. Myelin, which lends its color to the “white matter” of the brain, is a complex substance made up of at least ten different chemicals. Each of the leukodystrophies affects one (and only one) of these substances. CD is caused by mutations in the gene for an enzyme called aspartoacylase. Symptoms of CD, which appear in early infancy and progress rapidly, may include intellectual disability, loss of previously acquired motor skills, feeding difficulties, abnormal muscle tone (floppiness or stiffness), and an abnormally large, poorly controlled head. Paralysis, blindness, or hearing loss may also occur. Children are characteristically quiet and apathetic. Although CD may occur in any ethnic group, it is more frequent among Ashkenazi Jews from eastern Poland, Lithuania, and western Russia, and among Saudi Arabians.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10 CM CODING

Diagnostic testing: Diagnostic testing for CD may include:

  • CT and MRI scans showing abnormalities of the cerebral white matter (relatively spared cerebellum and brain stem white matter);

  • Urine gas chromatograhy-mass spectometry (GC-MS) finding of elevated N-acetylaspartic acid (NAA); and

  • Full gene sequence analysis of ASPA.

Physical findings: Physical findings for CD may include:

  • Macrocephaly (abnormally large head);

  • Hypotonia (low muscle tone);

  • Head lag in infants age three to five months of age or older;

  • Extremely poor head control;

  • Difficulty swallowing (dysphagia);

  • Delays in reaching developmental milestones;

  • Loss of abilities requiring mental and muscular activity (psychomotor regression);

  • Seizures;

  • Reflux;

  • Deterioration of optic nerves (optic atrophy);

  • Paralysis;

  • Blindness;

  • Hearing loss; and

  • Intellectual disability.

ICD-9: 330.0

ICD-10: E75.25

PROGRESSION

CD causes brain tissue atrophy cystic cavities resulting in enlargement of the brain and head size. The prognosis for CD is poor. Death usually occurs before age 4.

TREATMENT

There is no cure, nor is there a standard course of treatment. Treatment is symptomatic and supportive.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation: The diagnosis is confirmed by genetic testing revealing a mutation in the gene for the aspartoacylase enzyme.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets

110.08 B

Canavan disease confirmed by genetic testing or by laboratory testing for NAA.

111.17

Canavan disease confirmed by genetic testing or by laboratory testing for NAA.

Equals

110.08 B

Listing 110.08 requires that the impairment be established by genetic testing. In place of CD established by genetic testing, substitute CD established by typical history and neurological findings along with neuroimaging studies with cerebral abnormalities associated with CD.

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.141 Coffin-Lowry Syndrome

COMPASSIONATE ALLOWANCE INFORMATION

COFFIN-LOWRY SYNDROME

ALTERNATE NAMES

Coffin Syndrome; Coffin Lowry Disease; CLS

DESCRIPTION

Coffin-Lowry syndrome (CLS) is a condition that affects many parts of the body. The signs and symptoms are usually more severe in males than in females, although the features of this disorder range from very mild to severe in affected females.

Males with CLS typically have severe to profound intellectual disability and delayed development. Affected females may be cognitively normal, or they may have intellectual disability ranging from mild to profound. Beginning in childhood or adolescence, some people with this condition experience brief episodes of collapse when excited or startled by a loud noise. These attacks are called stimulus-induced drop episodes (SIDEs).

This condition is an inherited condition caused by mutations in the RSK2 and RPS6KA3 gene.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing:

  • Molecular testing of the RSK2 and RPS6KA3, the only genes yet published to be associated with CLS, can be used to confirm but not to rule out the diagnosis of typical CLS; and

  • Sequence analysis identifies mutations in approximately 35%-40% of probands.

Physical findings: Individuals with CLS may present with:

  • Distinctive facial features including a prominent forehead, widely spaced and downward slanting eyes, and short nose with a wide tip and a wide mouth with full lips;

  • Short stature;

  • An unusually small head (microcephaly);

  • Soft hands with short, tapered fingers;

  • Progressive abnormal curvature of the spine (kyphoscoliosis);

  • Unusual prominence of the breast bone;

  • Dental abnormalities; and

  • Heart and kidney involvement.

ICD-9: 759.89

ICD-10: Q89.8

PROGRESSION

The prognosis of people with CLS varies depending on the severity of symptoms and signs. Cardiac abnormalities may be present and may contribute to premature death.

TREATMENT

There is no cure and no standard course of treatment for CLS. Benzodiazepine medication is sometimes prescribed. Treatment is symptomatic and supportive, and may include physical and speech therapy and educational services.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

  • Clinical history and examination that describes the diagnostic features of the impairment, as well as the related functional limitations;

  • Genetic testing for mutations in the RSK2 and RPS6KA3 gene; and

  • Developmental assessment or psychological testing to address allegations of mental impairments may be warranted.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets

12.05

Listing level physical or cognitive severity must be documented; the diagnosis or laboratory testing alone does not meet listing severity.

112.05

Listing level physical or cognitive severity must be documented; the diagnosis or laboratory testing alone does not meet listing severity.

Equals

110.08

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.143 Congenital Myotonic Dystrophy

COMPASSIONATE ALLOWANCE INFORMATION

CONGENITAL MYOTONIC DYSTROPHY

ALTERNATE NAMES

Steinert’s Disease; Myotonic dystrophy type 1

DESCRIPTION

Congenital Myotonic Dystrophy (type 1) is the most severe form of myotonic dystrophy, a rare, inherited neurlogical disorder caused by a mutation of the DMPK gene. Signs and symptoms are apparent after birth. These can include severe muscle weakness resulting in respiratory insufficiency, dysphagia leading to aspiration pneumonia, cardiomyopathy, and failure to thrive. Developmental delays are common. Later complications may include excessive daytime sleepiness, intellectual disability, autism, and ADHD. If the child survives to adulthood, he/she will start to take on the symptoms commonly seen in adult myotonic dystrophy type 1 as well.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: Congenital myotonic dystrophy is difficult to recognize because there can be multiple causes of weakness and hypotonia in newborns. The diagnosis can be confirmed through:

  • Molecular genetic testing;

  • Electromyography (EMG);

  • Muscle biopsy; and

  • Sometimes-elevated serum CK concentration.

Physical findings: Physical examination shows:

  • General muscle weakness, especially of the face and throat muscles;

  • Difficult or labored breathing (dyspnea);

  • Difficulty swallowing (dysphagia);

  • Ineffective nursing due to weak suck;

  • Slurred speech;

  • Extremity contractures;

  • Developmental delays;

  • Cardiomyopathy;

  • Failure to thrive;

  • Excessive daytime sleepiness;

  • Intellectual disability;

  • Autism; and

  • Attention deficit hyperactivity disorder (ADHD).

ICD-9: 395.21

ICD-10: G71.11

PROGRESSION

For congenital myotonic dystrophy, abnormal muscle weakness and other findings are present at birth. Progression occurs throughout the child’s lifetime; however, the rate and severity may vary, even with family members.

TREATMENT

Currently there is no cure for this disorder. Treatment is supportive and symptomatic.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

  • Clinical history and physical examination that describes the diagnostic features of the impairment; and

  • Genetic testing.

Suggested Listings for Evaluation:
DETERMINATION LISTING REMARKS
Meets 11.13 Listing-level severity must be documented.

111.13

Listing-level severity must be documented.
Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.145 Creutzfeldt-Jakob Disease (CJD)

COMPASSIONATE ALLOWANCE INFORMATION

CREUTZFELDT-JAKOB DISEASE (CJD) - Adult

ALTERNATE NAMES

Jakob-Creutzfeldt Disease; Jakobs Disease; Subacute Spongiform Encephalopathy; Variant (V-CJD) Bovine Spongiform Encephalopathy (BSE); Fatal Familial Insomnia (FFI); Gerstmann-Straussler-Scheinker (GSS) Disease; Prion disease

DESCRIPTION

Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, invariably fatal brain disorder primarily characterized by mental deterioration, although motor problems can be significant in many cases. CJD belongs to a group of human and animal diseases known as transmissible spongiform encephalopathies (TSE) or prion diseases. Spongiform refers to the characteristic appearance of infected brains, which become filled with holes until they resemble sponges under a microscope. Typically, onset of symptoms occurs at about age 60 and runs a rapid course. There are four major categories of CJD: sporadic CJD, hereditary CJD, acquired or iatrogenic CJD, and variant CJD.

Sporadic CJD is the most common form of the disease. It accounts for 85% of cases. The cause of sporadic CJD is unknown, but it is believed that a normal cellular protein undergoes a spontaneous change in conformation (prion protein) that results in the disease. This form of the disease is believed to be spontaneous and not the result of an infection.

Hereditary or familial CJD is a very uncommon disease and the consequence of a mutation in the gene that encodes the prion protein. About 5 to 10 percent of cases of CJD in the United States are hereditary.

Acquired or Iatrogenic CJD is also very rare accounting for less than 1% of cases. It results from the accidental transmission during the course of medical interventions. Examples include transmission in cases of corneal transplantation, dural grafts, or treatment with Human Growth Hormone isolated from cadaveric pituitary glands.

Variant CJD was first reported in 1996. It is believed to be the result of eating meat from cattle with bovine spongiform encephalopathy (BSE or mad cow disease). In contrast with sporadic CJD which affects older people, the variant form primarily affects young subjects (i.e., in the late 20s) and may have a longer course, between one and two years.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing:

  • Electroencephalography (EEG);

  • Magnetic resonance imaging (MRI) of the brain;

  • Cerebrospinal fluid analysis for 14-3-3 protein;

  • Tonsil biopsy is helpful in the diagnosis of variant CJD, but less so in other forms of the disease; and

  • Brain biopsy.

Brain biopsy is the definite diagnostic test, but is performed only in selected cases because the procedure may be dangerous to the individual. Since a correct diagnosis of CJD does not help the individual, brain biopsy is discouraged unless it is needed to rule out a treatable disorder.

Physical findings:

  • Rapidly progressing dementia with myoclonus (twitching);

  • Problems with muscle coordination;

  • Personality changes (impaired memory, judgement, and thinking);

  • Impaired vision;

  • Insomnia; and

  • Depression.

ICD-9: 046.19

ICD-10: A81.0

PROGRESSION

About 90 percent of patients die within 1 year. In the early stages of disease, patients may have failing memory, behavioral changes, lack of coordination and visual disturbances. As the illness progresses, mental deterioration becomes pronounced and involuntary movements, blindness, weakness of extremities, and coma may occur.

TREATMENT

There is no treatment that can cure or control CJD. Current treatment is aimed at alleviating symptoms and making the patient as comfortable as possible. Opiate drugs can help relieve pain, and the drugs clonazepam and sodium valproate may help relieve involuntary muscle jerks.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

  • Clinical notes and results of neurological examination that establish the presence of rapidly progressive dementia or neurodegenerative illness; and

  • If available, ancillary studies, including spinal tap, cerebrospinal fluid analysis, detection of 14-3-3 protein in spinal fluid, EEG, and brain biopsy are helpful as supportive evidence.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets

11.17

Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.160 Farber's Disease

COMPASSIONATE ALLOWANCE INFORMATION

FARBER’S DISEASE (FD) – Infantile

ALTERNATE NAMES

Acid Ceramidase Deficiency; Disseminated Lipogranulomatosis; Farbers Syndrome; Farber disease; Farber lipogranulomatosis

DESCRIPTION

Farber's disease (FD) is a rare inherited condition involving the breakdown and use of fats in the body (lipid metabolism). Affected children have an abnormal accumulation of lipids (fat) throughout the cells and tissues of the body, particularly around the joints. There are 7 different types of FD. Infantile FD type 1 and FD type 4 are the most severe.

The disease occurs when both parents carry and pass on the defective gene that regulates the lipid-protein sphingomyelin. Children born to these parents have a 25 percent chance of inheriting the disorder and a 50 percent chance of carrying the faulty gene. The disorder affects both males and females.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: Diagnosis of FD is confirmed by:

  • Laboratory findings of acid ceramidase activity, which is less than 6 percent of control values, measured in cultured skin fibroblasts (connective tissue cells), white blood cells or amniocytes.

  • Clinical findings (evidence) on biopsy showing granulomas with macrophages containing lipid cytoplasmic inclusions in subcutaneous nodules (masses or lumps under the skin) or other tissues; and

  • Laboratory confirmation of ceramide accumulation in tissues by chromatography or mass spectrometry is also an established diagnostic test for FD.

Physical findings: FD is characterized by 3 classic symptoms:

  • Hoarse voice or weak cry;

  • Small lumps of fat under the skin and in other tissues (lipogranulomas); and

  • Swollen and painful joints.

Other symptoms may include:

  • Difficulty breathing;

  • Enlarged liver and spleen (heptasplenomegaly);

  • Cardiac, pulmonary, and neurological defects;

  • Progressive neurological deterioration;

  • Seizures;

  • Paraparesis (leg paralysis);

  • Developmental delay;

  • Hydrops fetalis;

  • Lethargy; and

  • Failure to thrive.

ICD-9: 272.8

ICD-10: E75.6
PROGRESSION Limited neurodevelopment in the first year of life. Most children with Infantile FD type 1 and FD type 4 die by age 2, usually from lung disease.

TREATMENT

Currently there is no specific treatment for FD. Corticosteroids can help relieve pain. Nodes can be treated with bone marrow transplants, in certain instances, or may be surgically reduced or removed. There is no treatment for the progressive neurologic and developmental impairments.

SUGGESTED PROGRAMMATIC ASSESSMENT*
Suggested MER for Evaluation:
  • Results of acid ceramidase enzyme activity measured in cultured skin fibroblasts, white cells or amniocytes;

  • Other confirmatory lab tests for FD include reports that address typical histopathology features on biopsy and evidence of ceramide accumulation by chromatography of mass spectrometry; and

  • Clinical description of the physical and developmental findings support the diagnosis.

Suggested Listings for Evaluation:
DETERMINATION

LISTING

REMARKS

Meets 103.02 Tracheostomy in a child under 3 years.

110.08

FD type 1 or 4 with laboratory confirmation of the diagnosis. The listing requires developmental findings consistent with FD type 1 or type 4 and confirmation of the diagnosis by results of acceptable laboratory test(s).
111.17
Equals 114.09

Diagnosis of FD with findings described in the listing.

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.165 Friedreich's Ataxia (FRDA)

COMPASSIONATE ALLOWANCE INFORMATION

FRIEDREICH'S ATAXIA (FRDA)

ALTERNATE NAMES

Friedreich's Disease; Friedreich's Tabes; Hereditary Ataxia-Friedreich's type; Hereditofamilial Spinal Ataxia; Friedreich Ataxia; FA

DESCRIPTION

Friedreich's Ataxia (FRDA) is an inherited neurodegenerative disease that causes progressive damage to the nervous system resulting in symptoms ranging from muscle weakness and speech problems to heart disease. Ataxia results from the degeneration of nerve tissue in the spinal cord and of nerves that control muscle movement in the arms and legs. Symptoms usually begin between the ages of 5 and 15 but can appear as early as 18 months or as late as 30 years of age.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: Diagnosis of FRDA may be confirmed by:

  • Nerve conduction studies;

  • Electromyogram (EMG);

  • Electrocardiogram (EKG);

  • Magnetic Resonance Imaging (MRI);

  • Blood tests and urinalysis; and

  • Holter monitor.

Genetic testing can confirm the chromosomal abnormality that causes this disease. Evidence of positive gene testing and gait ataxia is necessary to determine the underlying gene abnormality that results in this disease to confirm the diagnosis of FRDA.

Physical findings:

  • Ataxia (lack of voluntary coordination of muscle movements);

  • Foot deformities, such as clubfoot, flexion (involuntary bending) of the toes, hammer toes, or foot inversion (turning in);

  • Nystagmus (rapid, rhythmic, involuntary movements of the eyeball);

  • Scoliosis (a curving of the spine to one side);

  • Chest pain;

  • Shortness of breath; and

  • Heart palpitations.

ICD-9: 334.0

ICD-10: G11.1

PROGRESSION

The FRDA gene is present at birth. Generally, within 15 to 20 years after the appearance of the first symptoms, the person is confined to a wheelchair, and in later stages of the disease, individuals become completely incapacitated. Most people with FRDA die in early adulthood if there is significant heart disease, the most common cause of death. Some people with less severe symptoms live much longer.

TREATMENT

There is currently no effective cure or treatment for FRDA. However, many of the symptoms and accompanying complications can be treated to help patients maintain optimal functioning as long as possible. Diabetes and heart problems can be treated with medications. Orthopedic problems such as foot deformities and scoliosis can be treated with braces or surgery. Physical therapy may prolong use of the arms and legs.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

  • Genetic testing for the FRDA gene; and

  • Clinical evaluation with history and complete neurological examination.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets 11.17

111.17

Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.170 Frontotemporal Dementia (FTD), Pick's Disease - Type A

COMPASSIONATE ALLOWANCE INFORMATION

FRONTOTEMPORAL DEMENTIA (FTD), PICK'S DISEASE - Type A - Adult

ALTERNATE NAMES

Frontotemporal Lobar Degeneration; Dementia with Lobar Atrophy and Neuronal Cytoplasmic Inclusions; Diffuse Degenerative Cerebral Disease; Lobar Atrophy of the brain; Pick Disease of the brain-Type 1; Wilhelmsen-Lynch Disease; FTD

DESCRIPTION

Frontotemporal Dementia (FTD) describes a clinical syndrome associated with shrinking of the frontal and temporal anterior lobes of the brain. Originally known as Pick's disease, the name and classification of FTD has been a topic of discussion for over a century. The current designation of the syndrome groups together Pick's disease, primary progressive aphasia, and semantic dementia as FTD. The presence of abnormalities in the nerve cells of the brain, called Pick bodies, distinguishes frontal lobe dementia from other types of dementia. There is a strong genetic component to the disease; FTD often runs in families.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing:
  • Physical exam;

  • Clinical assessment and blood tests;

  • Neurological exam that checks awareness and responsiveness, vital signs, reflexes, sensory responses and coordination;

  • Neuropsychological testing, which assesses memory, ability to reason and judge, problem-solving skills and language skills;

  • Brain imagining, such as MRI and CT, may demonstrate shrinkage of the frontal and temporal lobes and also help exclude other causes of dementia such as strokes and brain tumors; and

  • PET and SPEC tomography testing may be used to evaluate brain activity.

Physical findings: The symptoms of frontotemporal dementia depend on the areas of the brain affected. Most can be divided into one of two categories: behavior or language.

Common behavioral symptoms of frontotemporal dementia may include:

  • Inappropriate actions;

  • Apathy, or lack of interest or enthusiasm in activities;

  • Lack of inhibition or restraint;

  • Neglect of personal hygiene and care; and

  • Compulsive behavior.

Common language-related symptoms of frontotemporal dementia include:

  • Difficulty speaking or understanding speech;

  • Language recall problems;

  • Loss of reading and writing skills; and

  • Difficulty with social interactions.

ICD-9: 331.1

ICD-10: G31.0

PROGRESSION

The outcome for individuals with FTD is poor. The disease progresses steadily and often rapidly, ranging from less than 2 years in some individuals to more than 10 years in others. Eventually some individuals with FTD will need 24-hour care and monitoring at home or in an institutionalized care setting.

TREATMENT

No treatment has been shown to slow the progression of FTD. Behavior modification may help control unacceptable or dangerous behaviors. Aggressive, agitated, or dangerous behaviors could require medication. Anti-depressants and tranquilizers have been shown to improve some symptoms.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

  • Brain imagining, such as MRI and CT, may demonstrate shrinkage of the frontal and temporal lobes and also help exclude other causes of dementia such as strokes and brain tumors;

  • PET and SPEC tomography testing may be used to evaluate brain activity;

  • Clinical evidence describing general physical and blood tests to rule out thyroid disease, vitamin B12 deficiency, and syphilis;

  • Consideration of family history is appropriate as there is often a strong family predisposition for FTD;

  • Documentation of a clinically appropriate medical history;

  • Neurological findings consistent with the diagnosis of FTD; and

  • The results of any electrophysiological and neuroimaging testing may be considered.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets 11.17

12.02

Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.181 Giant Axonal Neuropathy

COMPASSIONATE ALLOWANCE INFORMATION

GIANT AXONAL NEUROPATHY

ALTERNATE NAMES

GAN; Giant Axonal Disease

DESCRIPTION

Giant Axonal Neuropathy (GAN) is a rare inherited genetic disorder that affects both the central and peripheral nervous systems. GAN is caused by mutations in the GAN gene, the gene that provides instructions for making a protein called gigaxonin, an important protein in cellular development. The majority of children with GAN will begin to show symptoms of the disease sometime before five years of age. Signs of GAN usually begin in the peripheral nervous system, which controls movement and sensation in the arms, legs, and other parts of the body. The typical symptoms of GAN are clumsiness and muscle weakness that progresses from a “waddling gait” to a pronounced difficulty in walking. Additional symptoms include numbness or lack of feeling in the arms and legs, seizures, nystagmus (rapid back and forth movement of the eyes), and intellectual disability.  

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: The diagnosis of GAN is established by clinical findings including:

  • Nerve conduction velocity (NCV);

  • Lumbar puncture;

  • Brain magnetic resonance imaging (MRI);

  • Peripheral nerve biopsy; and

  • EEG (electroencephalogram).

A definitive diagnosis of GAN using genetic testing is available on a research basis.

Physical findings: Physical examination of GAN may reveal:

  • Low muscle tone;

  • Muscle weakness;

  • Decreased reflexes;

  • Impaired muscle coordination;

  • Impaired sensation; and

  • Developmental delay.

ICD-9: 356.0

ICD-10: G60.0

PROGRESSION

GAN usually appears in infancy or early childhood. GAN generally progresses slowly as neurons degenerate and die. Most children have problems with walking in the early stages of the disorder. Later they may lose sensation, coordination, strength, and reflexes in their arms and legs. As time goes on, the brain and spinal cord may become involved, causing a gradual decline in mental function, loss of control of body movement, and seizures. Most children become wheelchair dependent in the second decade of life. Some children may survive into early adulthood.

TREATMENT

There is no cure for this disorder. Treatment for GAN is symptom specific and supportive. Children with GAN usually work with a medical team consisting of a pediatric neurologist, orthopedic surgeon, physiotherapist, psychologist, and speech and occupational therapists. The primary goal of treatment is to maximize intellectual and physical development and improve adaptive functioning. Many children with GAN have normal intellectual development and are able to attend regular school. As the disease progresses neurological deterioration may occur. School age children may need to be monitored at least once a year to assess their intellectual abilities and signs of neurological deterioration.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

  • Clinical history and examination that describes the diagnostic features of the impairment and laboratory findings are needed to confirm the diagnosis.

  • Developmental assessment or psychological assessment to address allegations of mental impairment may be warranted.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets

11.17

Listing level neurological and/or cognitive findings must be documented; diagnosis of GAN or laboratory testing results alone does not meet listing severity.

111.17

Listing level neurological and/or cognitive findings must be documented; diagnosis of GAN or laboratory testing results alone does not meet listing severity.

Equals

111.02

Must satisfy listing-level severity.

112.02

Must satisfy listing-level severity.

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.190 Head and Neck Cancers

COMPASSIONATE ALLOWANCE INFORMATION
HEAD AND NECK CANCERS

ALTERNATE NAMES

Squamous Cell Carcinoma of the nasal cavity, sinuses, lips, mouth, nose, tonsils, tongue, throat, or larynx (voice box); Adenocarcinoma of the nasal cavity, sinuses, lips, mouth, nose, tonsils, tongue, throat, or larynx (voice box); Squamous Cell Cancer of the nasal cavity, sinuses, lips, mouth, nose, tonsils, tongue, throat, or larynx (voice box); Metastatic Squamous Cell Neck Cancer; Metastatic Squamous Cell Neck Carcinoma; Head and Neck Carcinomas; Small Cell or Oat Cell Carcinoma

DESCRIPTION

Head and Neck Cancers includes those cancers that arise in the head or neck region (e.g., nasal cavity, sinuses, lips, mouth, tongue, throat, or larynx [voice box]).

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: The following may be used to diagnose the disease:

  • Physical exam and history;

  • Endoscopy;

  • Laboratory tests including blood and urine analysis;

  • X-rays;

  • Computed tomography (CT) scan;

  • Biopsy;

  • Magnetic resonance imaging (MRI); and

  • Positron emission tomography (PET) scan.

Physical findings:

  • Persistent sore throat;

  • Mouth sores that won't heal;

  • Hoarseness;

  • Persistent swelling of the neck

ICD-9: 173.02,

ICD-10: C30, C44.40, C80.1

PROGRESSION

When cancer of any of the sites is advanced, the prognosis is very poor.

TREATMENT

Treatment may include surgery, radiation, and/or chemotherapy. These treatments may affect eating, speaking, or even breathing.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation: A pathology report and an operative report are the preferred methods for documentation. In the absence of these reports, the adjudicator may use a physician's opinion that indicates the cancer is inoperable or unresectable based on described objective findings. "Inoperable" refers to a physician's opinion that surgery would not be beneficial based on a review of imaging studies, laboratory results, and physical examination findings. "Unresectable" cancer is established when the operative report indicates that the cancer is not completely removed or the pathology report notes that the surgical specimen has positive margins.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets

13.02

Head and Neck Cancer that is inoperable or unresectable, has distant metastasis, or is a small cell (oat cell) carcinoma, meets the requirements in listing 13.02.

Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.191 Hoyeraal-Hreidarsson Syndrome

COMPASSIONATE ALLOWANCE INFORMATION
HOYERAAL-HREIDARSSON SYNDROME

ALTERNATE NAMES

Hoyeraal-Hreidarsson Disease; Cerebellar Hypoplasia with Pancytopenia; Progressive Pancytopenia Immunodeficiency Cerebellar Hypoplasia

DESCRIPTION

Hoyeraal-Hreidarsson Syndrome (HHS) is a severe X-linked multi-system disorder caused by mutations in the DKC1 gene.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing:

  • Neuroimaging reports showing cerebellar hypoplasia/atrophy, small brainstem, thin corpus callosum and cerebral calcifications; and

  • Genetic testing for the DKC1.

Physical findings: Individuals with HHS are at risk for:

  • Microcephaly;

  • Delays in intrauterine growth;

  • Intellectual disability;

  • Spastic paresis (weakness or partial loss of voluntary movement);

  • Ataxia (impaired coordination);

  • Immunodeficiency;

  • Progressive bone marrow failure;

  • Myelodysplastic syndrome or acute leukemia;

  • Solid tumors of the head/neck;

  • Pulmonary fibrosis;

  • Hyperpigmentation (darkened patches or spots on the skin) of upper chest/neck;

  • Nail dystrophy;

  • Oral and premalignant leukoplakia affecting oral and gastrointestinal mucosa;

  • Eye abnormalities;

  • Dental abnormalities;

  • Developmental delay;

  • Cerebellar hypoplasia;

  • Bilateral exudative retinopathy; and

  • Intracranial calcifications.

ICD-9: 284; 287.33

ICD-10: D61

PROGRESSION

HHS usually presents in early childhood and primarily affects males (X-linked disorder). The prognosis is poor due to the severity of the disease course. Progressive bone marrow failure occurs in over 80% of cases and is the primary cause of early mortality.

TREATMENT

There is no cure for this disorder. Treatment is symptom specific and supportive. Aplastic anemia and immunodeficiency are treated with bone marrow/stem cell transplantation. Supportive treatment for gastrointestinal complications and infections is required.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

  • Clinical history and examination that describes the diagnostic features of the impairment;

  • Laboratory studies including results of genetic testing; and

  • Neuroimaging results.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets

7.02

 

7.06

7.10

7.17

11.17

111.17

Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.195 Infantile Neuroaxonal Dystrophy (INAD)

COMPASSIONATE ALLOWANCE INFORMATION

INFANTILE NEUROAXONAL DYSTROPHY (INAD)
ALTERNATE NAMES Prenatal or Connatal Neuroaxonal Dystrophy; Seitelberger Disease; INAD

DESCRIPTION

Infantile Neuroaxonal Dystrophy (INAD) is a rare, inherited neurological disorder. It affects axons, the part of a nerve cell that carries messages from the brain to other parts of the body. While the basic genetic and metabolic causes are unknown, INAD is the result of an abnormal build-up of toxic substances in nerves that communicate with muscles, skin, and the conjunctive tissue around the eyes. INAD is an autosomal recessive disorder, which means that both parents must be carriers of the defective gene that causes INAD to pass it on to their child.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing:

  • Tissue biopsy of skin, rectum, nerves, or conjunctive tissue;

  • Onset of symptoms in the first 2 years of age; and

  • Electrophysiology (nerve conduction velocities).

Physical findings:

  • Loss of head control and ability to sit, crawl, or walk;

  • Deterioration in vision and speech;

  • Seizures; and

  • Distinctive facial deformities, including a prominent forehead, crossed eyes, an unusually small nose or jaw, and large, low-set ears.

ICD-9: 359.1

ICD-10: G71.09

PROGRESSION

INAD is a progressive disease. Once symptoms begin, they will worsen over time. Generally, a baby's development starts to slow down between the ages of 6 months to 3 years. The first symptoms may be slowing of motor and mental development followed by loss or regression of previously acquired skills. Rapid, wobbly eye movements and squints may be the first symptoms, followed by floppiness in the body and legs (more than in the arms). For the first few years, a baby with INAD will be alert and responsive, despite being increasingly physically impaired. Eventually, because of deterioration in vision, speech, and mental skills, the child will lose touch with its surroundings. Death usually occurs between the ages of 5 to 10 years.

TREATMENT

There is no cure for INAD and no treatment that can stop the progress of the disease. Treatment is symptomatic and supportive. Doctors can prescribe medications for pain relief and sedation. Physiotherapists and other physical therapists can teach parents and caregivers how to position and seat their child, and to exercise arms and legs to maintain comfort.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

  • Evidence of onset of condition in first 2 years of life;

  • Molecular genetic testing for PLA2G6 gene; and

  • Description of associated clinical findings (e.g., progressive psychomotor regression, optic atrophy, hypotonia).

Suggested Listings for Evaluation:

DETERMINATION

LISTINGS

REMARKS

Meets 110.08 B INAD confirmed by molecular genetic testing.

111.17

Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.202 Joubert Syndrome

COMPASSIONATE ALLOWANCE INFORMATION
JOUBERT SYNDROME

ALTERNATE NAMES

Agenesis of Cerebellar Vermis; Cerebello-Oculo-Renal Syndrome; Cerebellooculorenal Syndrome 1; Cerebelloparenchymal Disorder 4; Joubert-Bolthauser Syndrome; Joubert Syndrome and Related Disorders; Joubert Syndrome Type A; Pure Joubert Syndrome; Classic Joubert Syndrome; JS

DESCRIPTION

Joubert Syndrome (JS) is a rare genetic disorder of brain development that may affect many parts of the body. It is characterized by the absence or underdevelopment of the cerebellar vermis (a part of the brain that controls balance and coordination) and a malformed brain stem (connection between the brain and spinal cord). JS appears to be inherited in an autosomal recessive manner (meaning both parents must have a copy of the mutation) via mutation in a number of genes, including NPHP1, AHI1, and CEP290. JS typically has an autosomal X-linked recessive pattern of inheritance.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: The diagnosis for JS is established by a combination of:

  • Clinical examination and imaging studies of the midbrain and pons that resemble the characteristic molar tooth sign;

  • Genetic testing for mutations in the NPHP1, CEP290, AHI1, TMEM67 (MKS3), RPGRIP1L, CC2D2A, ARL13B, INPP5E, OFD1, TMEM216, KIF7, TCTN1, TCTN2, TMEM237, CEP41, TMEM138, C5orf42, TMEM231, or TCTN3 genes.

Physical findings: JS may be seen in isolation or may be related to several other disorders including retinal dystrophy, renal disease, and other abnormalities. Infants with JS may have:

  • Abnormally large head (macrocephaly);

  • Prominent forehead;

  • High rounded eyebrows;

  • Epicanthal folds;

  • Ptosis (drooping or falling upper eyelid);

  • Upturned nose with prominent nostrils;

  • Open mouth;

  • Tongue protrusion;

  • Rhythmic tongue motions;

  • Low-set and tilted ears;

  • Cerebellar and brain stem malformation resulting in "molar tooth" sign seen on imaging;

  • Hypotonia (decreased muscle tone) in infancy;

  • Respiratory problems;

  • Retinal dystrophy;

  • Renal disease;

  • Ocular colobomas (missing pieces of tissues in or around the eye);

  • Occipital encephalocele;

  • Hepatic fibrosis;

  • Polydactyl (extra fingers and toes);

  • Oral hamartomas (nodules of mature cells and tissues);

  • Seizures;

  • Rapid breathing (hyperpnea);

  • Decreased muscle tone (hypotonia);

  • Jerky eye movements (oculomotor apraxia);

  • Intellectual impairment; and

  • Inability to coordinate voluntary muscle movements (ataxia);

ICD-9: 759.89

ICD-10: G11.1

PROGRESSION

Prognosis for children with Joubert Syndrome depends on the severity of the condition. The prognosis for infants with JS depends on whether or not the cerebellar vermis is partially developed or entirely absent. In some cases, the cerebellar vermis is almost fully developed, resulting in mild symptoms. The mildest form of the disease often results in mild lapses in motor control and mild intellectual disability. These individuals can live full, productive lives with medical and familial support.

TREATMENT

There is no definitive treatment available for JS. Treatment is supportive and symptom specific. Infants and children with abnormal breathing may require stimulatory medications; supplemental oxygen; mechanical support; or tracheostomy in rare cases. Other interventions may include speech therapy; occupational and physical therapy; educational support including special programs for the visually impaired; and feedings by gastrostomy tube. Surgery may be required for polydactyl and symptomatic ptosis or strabismus. End-stage renal disease, liver failure or fibrosis is treated with standard medical approaches. Children may require annual evaluations of growth, vision, and liver and kidney function and, periodic neuropsychological and developmental testing.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

  • Clinical history and examination that describes the diagnostic features of the impairment and laboratory findings are needed to confirm the diagnosis; and

  • Developmental assessment or psychological testing to address allegations of mental impairment may be warranted.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets

111.07

111.17

112.05

Equals 112.02

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.207 Kleefstra Syndrome

COMPASSIONATE ALLOWANCE INFORMATION

KLEEFSTRA SYNDROME

ALTERNATE NAMES

9q34 Deletion Syndrome; Chromosome 9q34.3 Deletion Syndrome; 9q34.3 Microdeletion Syndrome; 9q Subtelomeric Deletion Syndrome; 9qSTDS; 9q34.3 Terminal Deletion Syndrome

DESCRIPTION

Kleefstra syndrome is a disorder caused by terminal microdeletion of chromosome 9q34 involving loss of the EHMT1 gene, or by mutations that disable the function of the EHMT1 gene. Kleefstra syndrome involves many parts of the body including the brain, muscles, and bones.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: The diagnosis of Kleefstra syndrome is made by:

  • Physical examination;

  • Imaging studies of structural brain defects (e.g. microcephaly and brachycephaly); and

  • Is confirmed by the finding of abnormal EHMT1 sequencing.

Physical findings: Children with Kleefstra syndrome have recognizable facial stigmata. Other findings can include:

  • Developmental delay and intellectual disability;

  • Severely limited or absent speech;

  • Hypotonia (weak muscle tone);

  • Eyebrows that grow together in the middle (synophrys);

  • Widely spaced eyes (hypertelorism);

  • Sunken appearance of the middle of the face (midface hypoplasia);

  • Nostrils that open to the front rather than downward (anteverted nares);

  • Protruding jaw (prognathism);

  • Eolled out (everted) lips;

  • Large tongue (macroglossia);

  • Unusually wide and shortened (brachycephaly) or very small (microcephaly) skull;

  • Cardiac defects;

  • Urogenital/renal abnormalities;

  • Seizures; and

  • Tendency to develop severe respiratory infections.

ICD-9: 758.33

ICD-10: Q93.88

PROGRESSION

Onset is congenital. Children with Kleefstra syndrome may exhibit features of autism or related developmental disorders affecting communication and social interaction. In adolescence, they may develop a general loss of interest and enthusiasm (apathy) or extreme unresponsiveness (catatonia).

TREATMENT

Treatment of Kleefstra syndrome is supportive, and requires ongoing routine care by a multidisciplinary team specializing in the care of children or adults with intellectual disability. Referral to age-appropriate early childhood intervention program, special education, or vocational training. Therapies include speech/language therapy, physical and occupational therapy, and sensory integration. Extreme behavior problems may require treatment by a psychiatrist. Neurologic, cardiac, renal, urologic and other medical issues require standard monitoring and treatment. Medical follow-up is life-long.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

  • Clinical history and examination that describes the diagnostic features of the impairment;

  • Genetic testing for microdeletions at chromosome 9q34.3 or pathogenic mutations in the EHMT1 gene; and

  • Developmental assessment or psychological testing to address allegations of mental impairments may be warranted.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets

104.06

Listing-level severity must be documented; and evaluated under the most affected body systems.

111.09

Listing-level severity must be documented; and evaluated under the most affected body systems.

112.02

Listing-level severity must be documented; and evaluated under the most affected body systems.

112.05

Listing-level severity must be documented; and evaluated under the most affected body systems.
Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.210 Krabbe Disease (KD) - Infantile

COMPASSIONATE ALLOWANCE INFORMATION

KRABBE DISEASE (KD) - Infantile

ALTERNATE NAMES

Beta Galactocerebrosidase (GALC) Deficiency; Galactosylceramide Deficiency; Galactosylceramide Lipidosis; Globoid Cell Leukodystrophy (GLD); Krabbe Leukodystrophy; Sphingolipidoses, Krabbe type

DESCRIPTION

Krabbe disease (KD) is a rare, inherited degenerative disorder of the central and peripheral nervous systems. Krabbe disease is one of a group of genetic disorders called the leukodystrophies. These disorders impair the growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers, and cause severe degeneration of mental and motor skills. Myelin, which lends it color to the “white matter” of the brain, is a complex substance made up of at least 10 different enzymes. Each of the leukodystrophies affects one (and only one) of these substances. Krabbe disease is a lysomal storage disease caused by a deficiency of galactocerebrosidase (GALC), an essential enzyme for myelin metabolism.

Infantile form: This is the most common type and onset is almost always before 6 months of age and even during the first week of life. The baby usually dies within the first one or two years of life, most commonly due to infection and/or bulbar palsy.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: Before birth, a fetus can be screened for Krabbe disease. Using a needle, the doctor can withdraw amniotic fluid surrounding the fetus, and then the cells in this fluid can be examined in the lab. This requires obtaining fetal cells by chorionic villus sampling or culturing amniotic fluid cells obtained by amniocentesis. After birth, a physical exam of the child, evaluating signs and symptoms and diagnostic testing including: blood, skin (biopsy) samples, lumbar puncture (spinal tap), MRI and CT scans, nerve conduction studies, eye exam, and genetic testing may be done to confirm the diagnosis.

Physical findings:

  • Restlessness;

  • Intermittent fever;

  • Irritability and progressive stiffness (irritable-hypertonic presentation);

  • Fever without infection;

  • Convulsions may be part of the symptoms. There are also

  • Increased muscle tone and pyramidal signs;

  • Absent or weak deep tendon reflexes;

  • Rapid deterioration in motor function, with chronic opisthotonos and myoclonic jerking;

  • Hyperpyrexia, hypersalivation, and hypersecretion from the lungs; and

  • Rapid and severe motor and mental deterioration.

ICD-9: 330.0

ICD-10: E75.23

PROGRESSION

Infantile Krabbe disease is generally fatal before age 2. Prognosis may be significantly better for children who receive umbilical cord blood stem cells prior to disease onset or early bone marrow transplantation.

TREATMENT

There is no specific, proven treatment for advanced, symptomatic Krabbe disease. Treatment at this stage is designed primarily to ease symptoms. For example, anticonvulsant medications may be used to manage the seizures associated with this disease. Other drugs may reduce the risk of vomiting. Some research indicates possible benefits associated with the use of bone marrow transplantation or cord blood transfusion as treatments for Krabbe disease. For pre symptomatic infants and older individuals with mild symptoms, hematopoietic stem cell transplantation (HSCT) with cord blood provides a benefit over symptomatic treatment only.

SUGGESTED PROGRAMMATIC ASSESSMENT *
Suggested MER for Evaluation:
  • Genetic testing of GALC gene (targeted mutation or sequence analysis);

  • Enzyme assay for GALC enzyme activity;

  • MRI or CAT scan with characteristic white matter abnormalities; and

  • A description of motor findings (limb stiffness, spasticity, ataxia, progressive psychomotor decline).

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets 110.08 A Krabbe disease - infantile form confirmed by genetic testing or enzyme assay.

111.17

11.17

Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.220 Lesch-Nyhan Syndrome (LNS)

COMPASSIONATE ALLOWANCE INFORMATION

LESCH-NYHAN SYNDROME (LNS)

ALTERNATE NAMES

Hereditary Hyperuricemia and Choreoathetosis Syndrome; Hyperuricemia Choreoathetosis-Self mutilation Syndrome; Hyperuricemia-Oligophrenia; Hypoxanthine-Guanine Phosphoribosyltranferase Deficiency (HGPRT); Hypoxanthine phosphoribosyltransferase Deficiency (HPRT); Juvenile Gout-Choreoathetosis and Intellectual Disability Syndrome; Lesch Nyhan Disease; Nylan Syndrome

DESCRIPTION

Lesch-Nyhan syndrome (LNS) is a rare, inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). LNS is an X-linked recessive disease-- the gene is carried by the mother and passed on to her son. LNS is present at birth in baby boys (females are carriers of the gene). The lack of HPRT causes a build-up of uric acid in all body fluids, and leads to severe gout, poor muscle control, and moderate intellectual disability, which appear in the first year of life. Hypotonia and delayed motor milestones are usually evident by three to six months of age. The motor disability is so severe that virtually all children with LNS never walk and are confined to a wheelchair. Neurological signs include facial grimacing, involuntary writhing, and repetitive movements of the arms and legs similar to those seen in Huntington's disease. A striking feature of LNS is self-mutilating behaviors - characterized by lip and finger biting - that begin in the second year of life. Because a lack of HPRT causes the body to poorly utilize vitamin B12, some boys may develop a rare disorder called megaloblastic anemia.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: Molecular genetic testing is the most effective method of testing, as HPRT1 is the only gene known to be associated with LNS. Individuals who display the full Lesch-Nyhan phenotype all have mutations in the HPRT1 gene. Some consider the definitive confirmatory test to be the results of HPRT enzyme activity of less than 1.5% of normal blood or other type tissue cells.

Physical findings: Physical findings for LNS may include:

  • Psychomotor delay with a delay in head support and sitting;

  • Hypotonia (decreased muscle tone);

  • Athetoid (slow, involuntary, writhing movement of fingers, hands, toes, and feet) movements;

  • Sandy urine or crystalluria (cloudy urine caused by crystals) with urinary tract obstruction

  • Severe action dystonia (involuntary muscle contractions) with baseline hypotonia that may lead to an inability to stand up and walk;

  • Involuntary movements (choreoathetosis and ballismus) associated with voluntary movements increased by stress but not evident at rest;

  • Dysarthria (slurred or slow speech);

  • Dysphagia (difficulty swallowing);

  • Opisthotonus (nuscle spasms causing backward arching of the head, neck, and spine);

  • Spasticity;

  • Hyperreflexia (overactive or overresponsive reflexes) and extensor plantar reflex

  • Mild to moderate intellectual deficit;

  • Obsessive-compulsive self-mutilation (lip biting or finger chewing);

  • Aggressive behavior (i.e. spitting, abusive language);

  • Megaloblastic anemia;

  • Microcytic anemia;

  • Joint inflammation;

  • Gouty arthritis;

  • Urolithiasis (kidney stones); and

  • Renal failure or acidosis occur rarely.

ICD-9: 277.2

ICD-10: E79.1

PROGRESSION

The prognosis for individuals with LNS is poor. Death usually occurs in the first or second decade of life.

TREATMENT

Treatment for LNS is symptomatic. Gout can be treated with allopurinol to control excessive amounts of uric acid. Kidney stones may be treated with lithotripsy, a technique for breaking up kidney stones using shock waves or laser beams. There is no standard treatment for the neurological symptoms of LNS. Some may be relieved with the drugs carbidopa/levodopa, diazepam, phenobarbital, or haloperidol.

SUGGESTED PROGRAMMATIC ASSESSMENT*
Suggested MER for Evaluation: LNS is diagnosed by HPRT enzyme activity less than 1.5% of normal in tissue cells or genetic test results showing mutation in the HPRT1 gene and clinical description of the physical and developmental findings consistent with LNS.
Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets 110.08 Laboratory confirmed diagnosis of LNS that interferes very seriously with development.

111.17

Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.235 Metachromatic Leukodystrophy (MLD)

COMPASSIONATE ALLOWANCE INFORMATION

METACHROMATIC LEUKODYSTROPHY (MLD) - Late Infantile
ALTERNATE NAMES Arylsulfatase A Deficiency (ARSA); Cerebroside Sulfatase Deficiency; Metachromatic Form of Diffuse Cerebral Sclerosis; Metachromatic Leukoencephalopathy; Scholz-Bielchowsky-Henneberg Diffuse Cerebral Sclerosis; Scholz-Greenfield Disease; Sulphatide Lipidosis, Sulphatidosis; Van Bogaert-Nijssen Disease

DESCRIPTION

Metachromatic leukodystrophy (MLD) is a hereditary degenerative disease transmitted as an autosomal recessive, due to sulfatase A deficiency, with excess accumulation of sulfated lipids responsible for metachromasia in various tissues. MLD impairs the growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers

Late infantile form, which is the most common MLD, usually begins in the second year of life (ranges 1-3 years).

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: Diagnosis of MLD includes:

  • Magnetic resonance imaging (MRI) to identify lesions and atrophy in the white matter of the brain;

  • Urine tests usually show elevated sulfatide levels;

  • Some psychiatric disorders coupled with difficulty walking or muscle wasting; and

  • Blood testing can show a reduced activity of the ARSA enzyme.

Deficiency of the ARSA enzyme alone is not proof of MLD, because a substantial ARSA deficiency without any symptoms or clinical consequences is frequent in the general population. During diagnosis and genetic counseling, these harmless ARSA enzyme deficiencies must be distinguished from those causing MLD. The only diagnostic test that solves this problem and is definitive for MLD diagnosis is analysis of the genetic mutation.

Physical findings: After normal early development, the infant displays:

  • Irritability;

  • An unstable walk;

  • Developmental milestones, such as language development, are not met, and

  • Muscle wasting;

  • Spasticity;

  • Profound weakness;

  • Seizures;

  • Paralysis;

  • Dementia; and

  • Some children may become comatose.

ICD-9: 330.0

ICD-10: E75.25

PROGRESSION

No effective treatment is available to reverse the course of MLD. Drug therapy is part of supportive care for symptoms such as behavioral disturbances, feeding difficulties, seizures, and constipation. Bone marrow transplantation has been tried and there is evidence that this treatment might slow the progression of the disease. In infants, during a symptom-free phase of the late infantile form, neurocognitive function may be stabilized, but the symptoms of motor function loss progress.

TREATMENT

The prognosis for MLD is poor. In young children with MLD late infantile form, progressive loss of motor and cognitive functions is rapid. Death usually results within five years after the onset of clinical symptoms.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:
  • Genetic testing of ARSA gene (targeted mutation or sequence analysis;

  • Elevation of sulfatides (10 to 100 times normal) in 24-hour urine, enzyme assay for ARSA enzyme activity; and

  • MRI or CAT scan with characteristic white matter abnormalities and description of associated clinical findings (muscle weakness or wasting, rigidity developmental delays).

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets

110.08

Late infantile form of MLD confirmed by genetic testing or elevated sulfatides in 24-hour urine.

111.17

Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.250 Ornithine Transcarbamylase (OTC) Deficiency

COMPASSIONATE ALLOWANCE INFORMATION

ORNITHINE TRANSCARBAMYLASE (OTC) DEFICIENCY

ALTERNATE NAMES

Hyperammonemia Type II; Hyperammonemia due to Ornithine Transcarbamylase Deficiency; Ornithine Carbamyltransferase Deficiency

DESCRIPTION

Ornithine Transcarbamylase (OTC) Deficiency is a rare genetic disorder characterized by complete or partial lack of the enzyme ornithine transcarbamylase. OTC is one of six enzymes that play a role in the break down and removal of nitrogen from the body, a process known as the urea cycle. Accumulation of ammonium in the brain and blood usually follows a protein load or intermittent infection. OTC deficient patients are particularly sensitive to toxic effects of valproate.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM /ICD-10-CM CODING

Diagnostic testing: Laboratory confirmation of the gene defect is necessary.

  • Liver biopsy;

  • The combination of family history of the disorder, clinical presentation, plasma amino acid and urine orotic acid testing, and in some cases, molecular genetic testing are often sufficient for diagnostic confirmation, eliminating the risks of liver biopsy;

  • Presence of hyperammonemia;

  • Elavated urninary orotic acid;

  • Very low blood urea nitrogen (BUN) levels;

  • Blood ammonia studies;

  • Serum amino acid quantitation showing elevated ornithine, glutamine, and alanine levels and relatively low citrulline levels; and

  • Urine organic acid and amino acid analysis are helpful in ruling out other conditions.

Enzymatic deficiency of the ornithine transcarbamylase enzyme can be further confirmed with molecular diagnosis. However, even using a combination of different molecular analytic strategies, only 80% of proven enzymatic deficiencies can be shown to have genetic mutation.

Physical findings: In most cases the early symptoms appear within the first three days of life and include:

  • Respiratory distress;

  • Feeding difficulty;

  • Hypotonia (weak muscle tone);

  • Lethargy (lack of energy and enthusiasm);

  • Neonatal hyperammonemic coma lasting longer than 48 hours usually results in cortical atrophy and intellectual disability; and

  • Death in untreated cases.

ICD-9: 270.6

ICD-10: E72.4

PROGRESSION

Morbidity and mortality are high, especially in individuals with the neonatal form.

TREATMENT

  • Diet changes to discontinue protein intake is mandatory, with compensatory increases in carbohydrates and lipids in order to offset any catabolic tendency to draw on muscle amino acids for energy. Vegetarian diets are preferred because dietary protein intake often is associated with migraine-like headache.

  • Hemodialysis is used to achieve rapid reduction of extremely high blood ammonia levels (in some cases exceeding 2000 mg/dL) in comatose individuals.

  • Intravenous administration of sodium benzoate, arginine, and sodium phenylacetate in a large medical facility setting with close laboratory monitoring is a treatment form.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation: Clinical evaluation should include a description of physical and developmental findings, and current pediatric and neurological examination. Routine Laboratory tests will help rule out other disorders and MRI findings may be characteristic of ALX.
Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets

110.08

Laboratory and clinical findings consistent with OTC deficiency and progressive encephalopathy with or without treatment.

111.02

Laboratory and clinical findings consistent with OTC deficiency and progressive encephalopathy with or without treatment.

111.17

Laboratory and clinical findings consistent with OTC deficiency and progressive encephalopathy with or without treatment.

112.02

Laboratory and clinical findings consistent with OTC deficiency and progressive encephalopathy with or without treatment.

112.05

Laboratory and clinical findings consistent with OTC deficiency and progressive encephalopathy with or without treatment.
Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.261 Pallister-Killian Syndrome

COMPASSIONATE ALLOWANCE INFORMATION

PALLISTER-KILLIAN SYNDROME

ALTERNATE NAMES

Pallister Mosaic Syndrome; Pallister-Killian Mosaic Syndrome; Killian Syndrome; Teschler-Nicola/Killian Syndrome; Tetrasomy 12p Syndrome; Tetrasomy 12p Mosaic Syndrome; Isochromosome 12p Syndrome

DESCRIPTION

Pallister-Killian Syndrome (PKS) is a rare genetic disorder in which a person has four copies of the short arm of chromosome 12 (isochromosome 12p), instead of the normal two copies. The extra genetic material from isochromosome 12p disrupts the normal course of development, causing the characteristic features of this disorder.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: The diagnosis of PKS is made by physical examination and then confirmed by finding the presence of the extra genetic material of isochromosome 12p on a chromosome test.

Physical findings: Children with PKS have:

  • Extremely weak muscle tone (hypotonia);

  • Developmental delay/intellectual disability;

  • Distinctive facial features;

  • Sparse hair on the scalp;

  • Abnormally wide space between the eyes;

  • Extra skin folds over the corners of the eyes;

  • High arched or cleft palate;

  • Pale areas on the skin;

  • Hearing loss;

  • Vision impairment;

  • An extra nipple;

  • Genital abnormalities;

  • Heart defects; and

  • Skeletal abnormalities (i.e., extra fingers/toes, and unusually short arms and legs).

ICD-9: 759.89

ICD-10: Q99.8

PROGRESSION

Onset is congenital. Many infants with PKS die before they are born (that is, in utero) or soon after birth. Infants who survive birth have significant hypotonia, which can cause difficulty breathing and problems with feeding. Hypotonia also interferes with the normal development of motor skills, such as sitting, standing, and walking. About 30 percent of affected children are ultimately able to walk without assistance. Additional developmental delays result from intellectual disability, which is usually severe to profound. Speech is often limited or absent in children with this condition. About 40 percent of affected infants are born with a congenital diaphragmatic hernia, in which there is an abnormal opening in the diaphragm (the muscle that separates the abdomen from the chest cavity). This potentially serious birth defect allows the stomach and intestines to move into the chest, where they can crowd the developing heart and lungs. The physical manifestations of PKS progress with age. The prognosis for PKS is poor, although several people have been identified with mild intellectual disability and less obvious physical abnormalities.

TREATMENT

Treatment is dependent on the medical condition of the individual and the affected organ defects. Affected school age children may benefit from early intervention programs and special education.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

  • Clinical history and examination that describes the diagnostic features of the impairment; and

  • Laboratory tests showing results of genetic testing (chromosomal analysis).

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets 110.08

Listing-level severity must be documented; evaluate under the most affected body systems.

111.09

Listing-level severity must be documented; evaluate under the most affected body systems.

111.17

Listing-level severity must be documented; evaluate under the most affected body systems.

112.05

Listing-level severity must be documented; evaluate under the most affected body systems.

112.12

Listing-level severity must be documented; evaluate under the most affected body systems.
Equals
* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.280 Pompe Disease - Infantile

COMPASSIONATE ALLOWANCE INFORMATION

POMPE DISEASE - Infantile

ALTERNATE NAMES

Acid Maltase Deficiency (AMD); Alpha-1,4 Glucosidase Deficiency; Cardiomegalia Glycogenica Diffusa; Generalized Glycogenosis (Cardiac); Glycogen Storage Disease type II; Glycogenosis type II; Lysosomal Glucosidase Deficiency; Glycogen storage disease due to acid maltase deficiency, infantile onset

DESCRIPTION

Pompe disease is a rare (estimated at 1 in every 40,000 births) inherited and often fatal disorder that disables the heart and muscles. It is caused by mutations in a gene that makes an enzyme called alpha-glucosidase (GAA). Normally, the body uses GAA to break down glycogen, a stored form of sugar used for energy. But in Pompe disease, mutations in the GAA gene reduce or completely eliminate this essential enzyme. Excessive amounts of glycogen accumulate everywhere in the body, but the cells of the heart and skeletal muscles are the most seriously affected. Researchers have identified up to 70 different mutations in the GAA gene that cause the symptoms of Pompe disease, which can vary widely in terms of age of onset and severity. The severity of the disease and the age of onset are related to the degree of enzyme deficiency.

Infantile form occurs within the first months of life, with feeding problems, poor weight gain, muscle weakness, floppiness, and head lag. Respiratory difficulties are often complicated by lung infections. The heart is grossly enlarged. More than half of all infants with Pompe disease also have enlarged tongues.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: A diagnosis of Pompe disease can be confirmed by screening for the common genetic mutations or measuring the level of GAA enzyme activity in a blood sample - a test that has 100 percent accuracy.

Physical findings: Pompe disease usually presents within the first three months of life with:

  • Rapidly progressive muscle weakness (floppy infants)

  • Diminished muscle tone (hypotonia);

  • Respiratory insufficiency;

  • Large, protruding tongue (macroglossia);

  • Enlarged liver (hepatomegaly); and

  • Hypertrophic cardiomyopathy.

ICD-9: 271.0

ICD-10: E74.02

PROGRESSION

Most babies with the Infantile form of Pompe disease die from cardiac or respiratory complications before their first birthday. Without enzyme replacement therapy, the hearts of babies progressively thicken and enlarge.

TREATMENT

There is no cure for Pompe disease. Treatment, therefore, serves only to help minimize the symptoms. The clinical course is typically not affected by drugs that are used to treat the respiratory or cardiac defects. A high protein diet may be helpful and has led to significant improvements in respiratory function in some cases. An enzyme replacement therapy has been developed that has shown, in clinical trials with Infantile Pompe disease, to decrease heart size, maintain normal heart function, improve muscle function, tone, and strength, and reduce glycogen accumulation. A drug called alglucosidase alfa (Myozyme), has received FDA approval for the treatment of Pompe disease.

SUGGESTED PROGRAMMATIC ASSESSMENT*
Suggested MER for Evaluation: A diagnosis of Pompe disease can be confirmed by screening for the common genetic mutations or measuring the level of GAA deficiency in a blood sample - a test that has 100% accuracy.
Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets

104.02

This listing should be considered when definitive genetic testing is available or when the symptoms and signs that would meet this listing independent of the exact diagnosis are present.

110.08

This listing should be considered when definitive genetic testing is available or when the symptoms and signs that would meet this listing independent of the exact diagnosis are present.

111.17

This listing should be considered when definitive genetic testing is available or when the symptoms and signs that would meet this listing independent of the exact diagnosis are present.
Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.281 Progressive Bulbar Palsy

COMPASSIONATE ALLOWANCE INFORMATION

PROGRESSIVE BULBAR PALSY

ALTERNATE NAMES

Progressive Bulbar Atrophy; Bulbar Paralysis; Bulbar Palsy; Fazio-Londe Syndrome; Fazio-Londe Disease; Infantile Progressive Bulbar Palsy

DESCRIPTION

Progressive Bulbar Palsy (PBP) is a motor neuron disease that involves the brain stem—the bulb-shaped region containing lower motor neurons needed for swallowing, speaking, chewing, and other functions.  Symptoms include pharyngeal muscle weakness (involved with swallowing), weak jaw and facial muscles, progressive loss of speech, and tongue muscle atrophy. Limb weakness with both lower and upper motor neuron signs is almost always evident but less prominent. Individuals are at increased risk of choking and aspiration pneumonia, which is caused by the passage of liquids and food through the vocal folds and into the lower airways and lungs. Affected persons may have unusual outbursts of laughing or crying (called emotional lability). Stroke and myasthenia gravis may have certain symptoms that are similar to those of progressive bulbar palsy and must be ruled out prior to diagnosing this disorder. The exact cause of PBP is unknown.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: The diagnosis of PBP is based on:

  • History and neurological examination;

  • Electrophysiological and neuroimaging testing to rule out other impairments;

  • Needle electromyogram (EMG);

  • Nerve conduction study; and

  • Analysis of the cerebral spinal fluid to rule out other causes of symptoms.

Physical findings:

  • Spastic dysarthria (difficulties with articulation, stammering or stuttering);

  • Pseudobulbar reflexes; and

  • Pseudobulbar affect (uncontrollable crying or laughing).

ICD-9: 335.22

ICD-10: G12.22

PROGRESSION

The prognosis for PBP is poor. The symptoms of PBP slowly worsen with onset beginning between the ages of 50-70 years. Most people with PBP die from respiratory failure, usually within ten years from the onset of symptoms.

TREATMENT

Treatment of PBP is symptoms specific and supportive. Medications such as riluzole are prescribed to prolong survival. Other medications may be prescribed to help reduce fatigue, ease muscle cramps, control spasticity and reduce excess saliva and phlegm. A multidisciplinary team of health care professionals can design an individualized plan for medical and physical therapy and provide special equipment aimed at keeping the individual as mobile and comfortable as possible. As swallowing, tongue control, and pharyngeal muscles weaken, a speech therapist and nutritionist may be consulted.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

  • Clinical history and examination that describes the diagnostic features of the disorder;

  • Full neurological examination with emphasis on motor function and coordination, gait and balance, eye movements and gaze, and cognitive function; and

  • Brain imaging may provide supporting evidence.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets

11.17

11.22

111.17

111.22

Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.285 Rett Syndrome (RTT)

COMPASSIONATE ALLOWANCE INFORMATION
RETT SYNDROME (RTT)

ALTERNATE NAMES

MECP2 Related Disorder; RTT; RTS; cerebroatrophic hyperammonemia

DESCRIPTION

Rett syndrome (RTT), one of the MECP2 gene-related disorders, is a progressive neurologic disease in girls characterized by normal birth and apparently normal psychomotor development during the first six to 18 months of life. The girls then enter a short period of developmental stagnation followed by rapid regression in language and motor skills.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: The diagnosis of RTT rests on clinical diagnostic criteria established for the syndrome and/or molecular testing of the MECP2 gene. Molecular genetic testing identifies MECP2 mutations in approximately 80% of females with Rett syndrome.

Physical findings: RTT is characterized by:

  • Rapid developmental regression in infancy;

  • Loss of purposeful hand movements;

  • Screaming fits and inconsolable crying;

  • Bruxism (teeth grinding);

  • Tremors;

  • Loss of speech;

  • Gait abnormalities;

  • Repetitive stereotypic hand movements;

  • Severe intellectual disability;

  • Microcephaly;

  • Seizures;

  • Breathing abnormalities;

  • Disturbed sleeping patterns;

  • Scoliosis;

  • Impaired social interactions or social withdrawal;

  • Decreased mobility;

  • Muscle weakness;

  • Hand and foot deformities;

  • Rigidity;

  • Spasticity; and

  • Dystonia (involuntary muscle contractions).

ICD-9: 270.6

ICD-10: F84.2

PROGRESSION

Females with RTT may survive into adulthood, but in a very dependent state. The incidence of sudden, unexplained death is significantly higher than in controls of similar age and may in part be caused by the higher incidence of longer corrected QT intervals, T-wave abnormalities, and reduced heart rate variability.

TREATMENT

Currently there is no cure for RTT. Management is mainly symptomatic focusing on optimizing the individual’s abilities and providing psychosocial support for the family.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:
  • Molecular genetic testing with sequence analysis of the MECP2 gene on the X chromosome will identify 80% of individuals with Rett syndrome;

  • Additional clinical findings would show a characteristic decline or loss of previously attained developmental milestones (i.e., normal development for 6-18 months, followed by loss of milestones); and

  • A description of characteristic motor findings (repetitive hand movements, toe walking or unsteady, wide-based, stiff-legged gait) and severely impaired expressive language.

Suggested Listings for Evaluation:
DETERMINATION

LISTINGS

REMARKS

Meets 11.17

12.02

Mental dysfunction meeting the severity of these listings.

110.08

All claimants with clinical diagnostic criteria of Rett syndrome and abnormal molecular genetic testing of the MECP2 gene. (Positive genetic testing alone would not meet 110.08B).

111.17

112.02

Mental dysfunction meeting the severity of these listings.
Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.296 Seckel Syndrome

COMPASSIONATE ALLOWANCE INFORMATION

SECKEL SYNDROME

ALTERNATE NAMES

Seckel Type Dwarfism; Seckel Type Premordial Dwarfism; Microcephalic Primordial Dwarfism Seckel Type; Seckel Syndrome Types 1-4; Nanocephalic Dwarfism; Seckel syndrome type 1; Seckel syndrome type 2; Seckel syndrome type 3

DESCRIPTION

Seckel syndrome (SCKL) is a rare genetic disorder characterized by growth delays prior to birth (intrauterine growth retardation), and continuing growth delays after birth (postnatal). Seckel syndrome is inherited in an autosomal recessive fashion, and has been linked to genetic mutations on four different chromosomes.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: The diagnosis of SCKL is made by physical examination and confirmed by genetic testing.

Physical findings: The physical findings of SCKL include:

  • Small for gestational age at birth;

  • Extremely small but proportionate stature (dwarfism);

  • Small head size (microcephaly);

  • Pointed nose;

  • Narrow face;

  • Malformed ears;

  • High arched roof of the mouth (palate);

  • Tooth malformation;

  • Bony abnormalities such as unusually small jaw (micrognathia);

  • Permanent fixation of the fifth fingers in a bent position (clinodactyly);

  • Malformation (dysplasia) of the hips;

  • Dislocation of a bone in the forearm (radial dislocation); and,

  • Developmental delays.

ICD-9: 759.89

ICD-10: Q87.1

PROGRESSION

Developmental delays and intellectual disability tend to be severe. Hematological abnormalities, such as anemia, pancytopenia, and acute myeloid leukemia, are found in approximately 15 – 20% of children with this disorder.

TREATMENT

Treatment for SCKL is symptom specific. Affected school age children may benefit from early intervention programs and special education.

SUGGESTED PROGRAMMATIC ASSESSMENT

Suggested MER for Evaluation:

  • Clinical history and examination that describes the diagnostic features of the impairment; and

  • Laboratory tests showing results of genetic testing (chromosomal analysis).

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets 12.05 Listing level cognitive findings must be documented; diagnosis of SCKL or laboratory testing results alone does not meet listing severity.

100.02

Listing level growth or musculoskeletal findings must be documented; diagnosis of SCKL or laboratory testing results alone does not meet listing severity.

112.05

Listing level cognitive findings must be documented; diagnosis of SCKL or laboratory testing results alone does not meet listing severity.
112.12 Listing level cognitive findings must be documented; diagnosis of SCKL or laboratory testing results alone does not meet listing severity.
Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.297 Sjogren-Larsson Syndrome

COMPASSIONATE ALLOWANCE INFORMATION
SJÖGREN-LARSSON SYNDROME

ALTERNATE NAMES

Fatty Acid Alcohol Oxidoreductase Deficiency; FALDH Deficiency; Fatty Aldehyde Dehydrogenase Deficiency; Congenital Icthyosis Mental Retardation Spasticity Syndrome; Ichthyosis Spastic Neurologic Mental Retardation Disorder; Congenital Ichthyosis Oligophrenia and Spastic Paresis Syndrome; Ichthyosis Oligophrenia and Spastic Tetraplegia Syndrome; Ichthyosis Oligophrenia Syndrome

DESCRIPTION

Sjögren-Larsson Syndrome (SLS) is a rare, autosomal-inherited, cerebral palsy disorder. (SLS should not be confused with Sjögren syndrome, which is a different disorder.)

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: The diagnosis of SLS is confirmed by genetic testing for mutations in the ALDH3A2 gene.

Physical findings:

  • Ichthyosis (dry, scaly skin);

  • Developmental delay, including intellectual disability;

  • Delayed speech;

  • Delayed motor development;

  • Abnormal muscle stiffness (spasticity);

  • Seizures;

  • Glistening white dots at the back of the eye (retina);

  • Spastoc diplegia or tetraplegia; and

  • Nearsightedness (myopia).

ICD-9: 757.1

ICD-10: Q80

PROGRESSION

Developmental delays usually become apparent during the first 2 years of life. Spasticity is almost always present by age 2 years. Seizures typically develop later in childhood. No progression of the intellectual deficit occurs after puberty and any developmental skills, once gained, are usually maintained over time. However, if contractures progress, individuals may lose the ability to walk. About one-half of people with SLS require wheelchair assistance and many others need some form of support to walk.

Individuals with SLS usually survive well into adulthood but require life-long care. Life expectancy is determined by the severity of neurologic disorders. Morbidity is associated with chronic neurologic disease and lifelong ichthyosis.

TREATMENT

The pruritus associated with SLS is treated with topical moisturizing creams and keratolytic agents. Daily water baths help keep the skin hydrated. Seizures are treated with standard anticonvulsant medications.

SUGGEST PROGRAMMATIC ASSESSMENT
Suggested MER for Evaluation:
  • Clinical history and examination that describes the diagnostic features of the disorder;

  • Developmental assessment or psychological testing; and

  • Genetic testing showing mutations in ALDH3A2 gene.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets

11.02

Listing level neurological and/or cognitive findings must be documented; diagnosis of SLS or laboratory testing results alone does not meet listing severity. Do not confuse SLS with Sjögren syndrome.

11.17

Listing level neurological and/or cognitive findings must be documented; diagnosis of SLS or laboratory testing results alone does not meet listing severity. Do not confuse SLS with Sjögren syndrome.
12.05 Listing level neurological and/or cognitive findings must be documented; diagnosis of SLS or laboratory testing results alone does not meet listing severity. Do not confuse SLS with Sjögren syndrome.

111.02

Listing level neurological and/or cognitive findings must be documented; diagnosis of SLS or laboratory testing results alone does not meet listing severity. Do not confuse SLS with Sjögren syndrome.

111.17

Listing level neurological and/or cognitive findings must be documented; diagnosis of SLS or laboratory testing results alone does not meet listing severity. Do not confuse SLS with Sjögren syndrome.

112.05

Listing level neurological and/or cognitive findings must be documented; diagnosis of SLS or laboratory testing results alone does not meet listing severity. Do not confuse SLS with Sjögren syndrome.
Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.

DI 23022.300 Small Cell Cancer of the Large Intestine

COMPASSIONATE ALLOWANCE INFORMATION

SMALL CELL CANCER OF THE LARGE INTESTINE

ALTERNATE NAMES

Cancer of the Colon; Colorectal Small Cell Cancer; Small Cell Carcinoma of the Large Intestine

DESCRIPTION

Small Cell Cancer of the Large Intestine is an aggressive (fast-growing) cancer that forms in tissues of the intestine and can spread to other parts of the body. The cancer cells look small and oval-shaped when looked at under a microscope. Small cell carcinoma of the large intestine represents .2% to .8% of all colorectal malignancies.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: The diagnosis of colorectal small cell carcinoma is confirmed by pathology and the use of immunohistochemistry. Specific staining for CD56, pancytokeratin, LMWK, CK 7 and 19 are usually positive in small cell malignancies.

Early diagnosis depends on:

  • Routine screening;

  • Occult blood study;

  • Sigmoidoscopy;

  • Colonoscopy;

  • CT scan; and

  • Endoscopy.

Physical findings: General symptoms may include:

  • Change in bowel habits,

  • Abdominal pain; and

  • Weight loss.

ICD-9: 209.0

ICD-10: C7A.019
PROGRESSION

Survival rates are poor, usually less than 2 years.

TREATMENT

Treatment for colorectal small cell carcinoma is the use of combined chemotherapy and radiotherapy as is used in small cell carcinoma of the lung.

SUGGESTED PROGRAMMATIC ASSESSMENT*
Suggested MER for Evaluation: The diagnosis of small cell carcinoma of the large intestine is a pathologic diagnosis which would be confirmed by a pathology report of colonoscopy specimen.
Suggested Listings for Evaluation:
DETERMINATION LISTING REMARKS
Meets

13.18

Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or the listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.


DI 23022 TN 34 - Processing Quick Disability Determination (QDD) and Compassionate Allowance (CAL) in the Disability Determination Services (DDS) - 8/28/2020