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.
Aminoacylase-2 (ACY2) Deficiency, Aspartoacylase (ASPA) Deficiency, Canavan's Leukodystrophy, Spongy Degeneration of the Central Nervous System or Neuroaxis, Van Bogaert-Bertrand Syndrome
DIAGNOSTIC TESTING AND CODING
Clinical findings leading up to the diagnosis would include:
Physical findings including the triad of hypotonia (low muscle tone), macrocephaly (abnormally large head) and head lag in an infant age three to five months of age or older.
CT and MRI abnormalities of the cerebral white matter (relatively spared cerebellum and brain stem white matter).
Urine gas chromatography-mass spectrometry (GC-MS) finding of elevated N-acetylaspartic acid (NAA).
The test to confirm diagnosis is a full gene sequence analysis of ASPA. Gross deletion/duplication analysis of the entire ASPA gene is performed to detect known and potential novel gross deletions.