Effective Dates: 08/05/2026 - Present Previous | Next

TN 104 (08-26)

DI 23022.663 Adenylosuccinate Lyase Deficiency - Neonatal Form and Type 1

 

COMPASSIONATE ALLOWANCES INFORMATION

ADENYLOSUCCINATE LYASE DEFICIENCY - NEONATAL FORM AND TYPE 1

ALTERNATE NAMES

Adenylosuccinase Deficiency; Adenylosuccinate Lyase Deficiency Neonatal Form; Adenylosuccinate Lyase Deficiency Type 1; ADSLD; ADSL Deficiency; ADSL Deficiency Type 1; Succinylpurinemic Autism

DESCRIPTION

Adenylosuccinate lyase deficiency (ADSL deficiency) is a rare metabolic disorder caused by mutations in the ADSL gene and is inherited in an autosomal recessive fashion. It is characterized by developmental delay, seizures, learning/intellectual disability, and autism related behaviors.

The most severe forms of ADSL deficiency, based on the severity of the signs and symptoms, are:

  • •

    Neonatal form (most severe); and

  • •

    ADSL deficiency type 1 (severe and most common).

Neonatal form: The most severe type, with an onset from birth. It presents with fatal neonatal encephalopathy with a lack of spontaneous movement, respiratory failure, and intractable seizures resulting in early death within the first weeks of life.

ADSL deficiency type 1: Presents in infancy or early childhood with a purely neurologic clinical picture characterized by severe psychomotor retardation, microcephaly, early onset of seizures, and autistic features.

NOTE: ADSL deficiency type 2 is the moderate or mild form and has a later onset, usually within the first years of life, with slight to moderate psychomotor retardation and transient contact disturbances and will be evaluated on a case-by-case basis.

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

Diagnostic testing: Diagnostic testing for ADSL deficiency may include:

  • •

    Clinical examination;

  • •

    Cerebrospinal fluid (CSF) testing;

  • •

    Electroencephalogram (EEG);

  • •

    Genetic testing;

  • •

    Invitae epilepsy panel;

  • •

    Magnetic resonance imaging (MRI); and

  • •

    Urine and plasma analysis.

Physical findings: Signs and symptoms of ADSL deficiency vary based on the classified form.

Signs and symptoms of the neonatal form of ADSL deficiency may include:

  • •

    Floppy trunk with stiff limbs;

  • •

    Intractable seizures;

  • •

    Intrauterine growth restriction (IUGR);

  • •

    Involuntary muscle contractions (dystonia);

  • •

    Loss of fetal heart rate variability;

  • •

    Low level of fetal movement (hypokinesia);

  • •

    Poor coordination (ataxia);

  • •

    Respiratory failure; and

  • •

    Small head (microcephaly).

Signs and symptoms of ADSL deficiency type 1 may include:

  • •

    Absent or poor eye contact;

  • •

    Aggression onto oneself;

  • •

    Agitation;

  • •

    Epilepsy;

  • •

    Hyperactivity;

  • •

    Inappropriate laughter;

  • •

    Low muscle tone in the trunk of the body (axial hypotonia);

  • •

    Severe slowing of thought and movement (psychomotor impairment);

  • •

    Stereotypies (repetitive, rhythmic, and fixed movements or behaviors); and

  • •

    Tantrums.

ICD-9: 270.8; 275.8

ICD-10: E79.8; E79.9

PROGRESSION

Prognosis for ADSL deficiency in the neonatal and type 1 forms is poor.

Newborns with the neonatal form of ADSL deficiency have severe encephalopathy, which leads to a lack of movement, difficulty feeding, and life-threatening respiratory problems. Some affected newborns develop seizures that do not improve with treatment. Because of the severity of the encephalopathy, infants with this form of the condition generally do not survive more than a few weeks after birth.

Infants with ADSL deficiency type 1 develop recurrent seizures that are difficult to treat, and some exhibit autistic traits, such as repetitive actions and a lack of eye contact.

TREATMENT

Currently, there is no cure for any forms of ADSL deficiency. Treatment focuses on controlling seizures, although drug resistance can occur. Infants and newborns typically require a multidisciplinary approach involving neurologists, metabolic specialists, and other healthcare professionals to manage their symptoms and provide comprehensive care.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

  • •

    Clinical examination;

  • •

    Genetic testing;

  • •

    Imaging studies; and

  • •

    Laboratory test results.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets

111.02

112.02

112.05

112.10

112.11

112.14

 

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.
To Link to this section - Use this URL:
http://policy.ssa.gov/poms.nsf/lnx/0423022663
DI 23022.663 - Adenylosuccinate Lyase Deficiency - Neonatal Form and Type 1 - 08/05/2026
Batch run: 08/05/2026
Rev:08/05/2026