OMIM ID:
Canavan Disease
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Optic atrophy is the primary and perhaps only ocular manifestation of Canavan disease. Acuity levels have not been reported but it has been noted that some infants and young children with early onset severe disease are able to track targets. The ocular phenotype has not been well delineated.
Systemic Features
The clinical diagnosis of Canavan disease is suggested when the triad of hypotonia, macrocephaly and head lag is present. It is a progressive form of spongy degeneration of the central nervous system but its onset, course, and severity are variable.
The disease is often evident before 6 months of age and survival is limited to a few months or years in infants with such early onset. Such patients have the most severe and rapidly progressive disease. It is noteworthy that, even though such infants do not achieve normal milestones such as sitting and standing, they do often interact socially by laughing, smiling, and reaching for objects. Most young children are quiet and apathetic but some become irritable and develop spasticity as they grow. CNS damage is evident as leukodystrophy on neuroimaging studies but this may not be present in later onset, milder forms of the disease.
Other individuals may have a later and milder juvenile onset of symptoms and may present with delayed speech or motor development late in the first decade. They often attend regular school but may benefit from tutoring and speech therapy. They may live to adolescence or early adulthood. Maldevelopment of the organ of Corti is responsible for hearing deficits in some children.
Genetics
Inheritance
Canavan disease is an autosomal recessive disorder resulting from homozygous or compound heterozygous mutations in the gene (ASPA) located at 17p13.2 encoding the enzyme aspartoacylase. N-acetylaspartic acid (NAA) levels are usually elevated in urine. However, because the levels of NAA can vary depending on the severity of clinical disease, gene testing provides a more reliable diagnosis.
The carrier frequency is high among members of the Ashkenazi Jewish population.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.