At a Glance
Canavan disease (also known as ASPA Deficiency or N-AspartoacylaseDeficiency) is an inherited disorder of metabolism of the amino acidaspartic acid due to a defect in aspartocyclase leading to elevations ofN-acetylaspartic acid (NAA). Canavan disease is a severe, progressive,irreversible neurological disorder and is inherited in an autosomal recessive manner. Autosomal recessive inheritance means the individual has inherited 2 abnormal copies of the ASPA gene (each genecontaining a mutation). Both parents of an individual with Canavan disease are carriers and do not manifest any symptoms of disease.
Canavan disease typically presents in infants between 2 and 5 months with macrocephaly, hypotonia, and a head-lag. Leukodystrophy is found on magnetic resonance imaging (MRI). The disease gradually progresses, and children have developmental delay and are unable to develop the ability to sit and/or walk independently, but may be able to laugh and interact. They later develop spasticity, opisthotonis, difficulty sleeping, seizures, hearing loss, and optic nerve atrophy.
Other disorders with macrocephaly and developmental delay and leukodystrophy include Tay-Sachs disease, metachromatic leukodystrophy, glutaric academia type 1, and Alexander disease. Mitochondrial disease, such as in Leigh syndrome, or viral infections causing spongiform degeneration may also present in a similar manner.
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What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?
Diagnosis of Canavan disease can be made through demonstration of NAA on urine organic acid analysis. It is possible to measure NAA in blood and cerebral spinal fluid (CSF) but is not necessary.
Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?
Typically, levels of NAA will be 5-10 times normal, but mild elevations may be seen in Canavan disease, as well as other white matter diseases.
What Lab Results Are Absolutely Confirmatory?
Confirmation of Canavan disease can be attained through enzyme analysis and/or DNA sequencing. Aspartocyclase activity can be measured in skin fibroblasts and amniocytes.
Targeted sequencing is available for the common mutations in the Ashkenazi Jewish population. Two mutations are found in nearly 98% of Ashkenazi Jews. Another mutation has been reported in about one-half of non-Jewish populations, and full sequencing will detect about 90% of affected individuals.
Large gene deletions and duplications are thought to be found in the remaining individuals.
What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?
Treatment is based on supportive therapy of symptoms.
Individuals should have a comprehensive, multidisciplinary team to meet nutritional needs, including gastrostomy tube feedings, and to provide adequate physical and occupational therapy, special education, management of infectious disease, airway protection, and treatment of seizures.
There is no therapy currently available, although research with gene therapy and the use of glyceryl triacetate is currently underway.
Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?
Failure to demonstrate NAA will effectively rule out Canavan disease, but other causes of white matter disease, macrocephaly, and developmental disease should be considered.
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