Canavan disease (CD) is a rare, inherited neurological disorder that progressively damages nerve cells in the brain. It is classified as a leukodystrophy, affecting the white matter, which is the protective coating around nerve fibers. This deterioration is caused by a failure to produce a specific enzyme, leading to a buildup of a substance that interferes with normal brain function. Early identification is important for initiating supportive care and exploring therapeutic options.
Recognizing Clinical Indicators
The diagnostic process begins with observing specific developmental signs in infants, typically appearing between three and six months of age. Children often fail to meet motor milestones, such as lifting their head or sitting without support. This lack of motor skill acquisition is often accompanied by hypotonia, which is reduced muscle tone or floppiness.
Another common sign is macrocephaly, an abnormally large head size that develops rapidly. These clinical findings, including developmental delays and poor head control, prompt investigation into underlying neurological causes. While these signs are not exclusive to Canavan disease, their combination in early infancy suggests the need for specific diagnostic testing.
Biochemical Testing for NAA Levels
Once clinical suspicion is established, biochemical analysis detects the disease’s metabolic signature. Canavan disease results from a deficiency of the enzyme aspartoacylase (ASPA), which normally breaks down the brain chemical N-acetylaspartate (NAA). Without sufficient ASPA activity, NAA accumulates to abnormally high levels throughout the central nervous system.
The hallmark finding is the elevated concentration of NAA in bodily fluids, serving as a reliable diagnostic marker. Physicians often use organic acid analysis of a urine sample as the first, non-invasive screening tool. This test detects significantly increased NAA levels, confirming clinical suspicion. High NAA levels are considered pathognomonic, meaning they are characteristic and virtually diagnostic of Canavan disease, distinguishing it from other leukodystrophies.
Definitive Genetic Confirmation and Screening
While elevated NAA levels strongly indicate the condition, definitive diagnosis requires molecular genetic testing to identify the causative mutations. This testing focuses on the ASPA gene on chromosome 17, which codes for the aspartoacylase enzyme. Analyzing a blood or saliva sample confirms the presence of two pathogenic variants, one inherited from each parent, establishing the diagnosis.
Genetic analysis is also used for carrier screening, especially for prospective parents with a family history or those of Ashkenazi Jewish heritage, where specific founder mutations are common. Carrier screening determines if a parent carries a single copy of the mutated ASPA gene. If both parents are carriers, prenatal diagnosis can be performed to test the fetus for the specific gene mutations.