Program Operations Manual System (POMS)
TN 16 (03-18)
DI 23022.095 Alexander Disease
COMPASSIONATE ALLOWANCE INFORMATION
ALEXANDER DISEASE (ALX) - Neonatal and Infantile
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.
Alexander Syndrome, Dysmyelogenic Leukodystrophy, Dysmyelogenic Leukodystrophy-Megalobare, Fribrinoid Degeneration of Astrocytes-Infantile type, Fibrinoid Leukodystrophy-Infantile type, Hyaline Panneuropathy, Leukodystrophy with Rosenthal Fibers, Megalencephaly with Hyaline Inclusion, Megalencephaly with Hyaline Panneuropathy
DIAGNOSTIC TESTING AND CODING
A diagnosis of Alexander disease is usually based on radiologic studies including MRI, CT scan or Ultrasound. An MRI of an individual with the infantile form typically reveals white matter loss that involves the frontal lobes of the brain, abnormalities of the basal ganglia and thalamus, possibly, enlargement of the ventricles. Genetic testing is accomplished by looking for known or detectable mutations in the GFAP gene. In up to 94% of cases of ALX, a GFAP mutation is found. Prenatal diagnosis for couples with an affected child can be performed when the mutation responsible for ALX is known. The DNA of a fetus can be tested using cells obtained from chorionic villus sampling (CVS) or amniocentesis.
Prior to the discovery of the gene responsible for the disease, diagnosis of ALX was made by demonstration of Rosenthal fibers in a biopsy or autopsy sample from the brain. Though genetic testing has largely replaced these histologic studies, a brain biopsy or autopsy may be indicated in select cases if the diagnosis cannot be made through other means.
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.
The prognosis for ALX is generally poor. Most children with the infantile form do not survive past the age of 6.
SUGGESTED PROGRAMMATIC ASSESSMENT*
Suggested MER for Evaluation: Clinical evaluation should include a complete history and a detailed, 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:
ALX (neonatal) with confirmed molecular genetic testing.
ALX (infantile) with confirmed molecular genetic testing.
* Adjudicators may, at their discretion, use the Medical Evidence of Record or Listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.