Canavan disease is a rare, severe neurological disorder that damages nerve cells and the brain’s white matter. It is a type of leukodystrophy, genetic disorders affecting the growth or maintenance of the myelin sheath.
Understanding Canavan Disease
Canavan disease stems from a genetic alteration in the ASPA gene, located on chromosome 17. This gene provides instructions for creating an enzyme called aspartoacylase (ASPA). Aspartoacylase is responsible for breaking down a brain chemical known as N-acetylaspartate (NAA) into acetate.
When the ASPA gene is mutated, the aspartoacylase enzyme becomes deficient. This deficiency leads to an accumulation of NAA in the brain. The buildup of NAA is thought to interfere with the formation and maintenance of myelin, the fatty insulating sheath that surrounds nerve fibers. Without properly formed myelin, nerve cells cannot communicate effectively, leading to the progressive neurological symptoms observed in Canavan disease.
Prevalence and Inheritance
Canavan disease is considered a rare disorder globally. In the non-Jewish population, incidence is about 1 in 100,000 births. While it can affect individuals from any ethnic background, it is significantly more common within specific populations.
The disease shows a notably higher prevalence among Eastern European (Ashkenazi) Jewish individuals. In this population, the incidence ranges from about 1 in 6,400 to 1 in 13,500 births. Carrier frequency among Ashkenazi Jewish individuals is also higher, with approximately 1 in 40 to 1 in 58 individuals being carriers. This increased prevalence in a specific group is often attributed to a “founder effect,” where certain genetic mutations become more concentrated in a population due to a small number of original ancestors.
Canavan disease follows an autosomal recessive inheritance pattern. This means an individual must inherit two mutated ASPA genes, one from each parent, to develop the condition. Parents with one mutated gene and one functional gene are asymptomatic carriers, meaning they do not show symptoms of the disease themselves. When two carrier parents have a child, there is a 25% chance with each pregnancy that the child will inherit two mutated genes and be affected by Canavan disease. There is also a 50% chance the child will be an asymptomatic carrier, and a 25% chance the child will inherit two functional genes and be neither affected nor a carrier.
Genetic Screening and Diagnosis
Genetic screening is important, particularly for individuals with a family history of Canavan disease or those from higher-risk ethnic backgrounds. Carrier screening involves analyzing a small blood or saliva sample to identify mutations in the ASPA gene. If both prospective parents are identified as carriers, genetic counseling can provide information about reproductive options and risks for future pregnancies.
For pregnancies where both parents are known carriers or there is a high risk, prenatal diagnosis is available. This can be performed through amniocentesis, typically between 15 to 20 weeks of pregnancy, which measures NAA levels in the amniotic fluid. Chorionic villus sampling (CVS), performed earlier between 10 to 12 weeks, can also test placental tissue for the genetic mutation.
For infants exhibiting symptoms, diagnosis often begins with clinical findings such as poor head control, developmental delays, and an abnormally large head. Diagnostic methods include urine tests that detect very high concentrations of NAA, or specialized brain scans like magnetic resonance spectroscopy that can show elevated NAA levels in the brain. Genetic testing to identify ASPA gene mutations confirms the diagnosis.