CANAVAN DISEASE (CD)

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

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: 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

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.

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.

REMARKS

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

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

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.