Canavan Disease (CD) is a rare, progressive neurological disorder that primarily affects the central nervous system. It is classified as a leukodystrophy, a group of genetic conditions that disrupt the growth or maintenance of the myelin sheath. Myelin is the fatty white matter that insulates nerve fibers, and its degeneration impairs the brain’s ability to transmit signals efficiently. The disorder typically presents in infancy, leading to developmental delay, a decline in motor skills, and the progressive loss of white matter.
The Genetic Basis of Canavan Disease
Canavan Disease is caused by a mutation in the ASPA gene, located on chromosome 17. This gene provides instructions for making the enzyme aspartoacylase, a protein primarily found in specialized brain cells. Aspartoacylase’s function is to break down N-acetylaspartate (NAA) into aspartate and acetate.
When the ASPA gene is mutated, the enzyme becomes deficient or non-functional, causing NAA to accumulate to toxic levels in the brain. This excessive buildup is associated with the progressive destruction of the white matter. The resulting degeneration of myelin disrupts communication between nerve cells, causing the severe neurological symptoms characteristic of CD.
Global Prevalence and Incidence Rates
Canavan Disease is a very rare condition globally, but its frequency varies dramatically depending on the population studied. The incidence of the severe, infantile form in the general, non-Jewish population is estimated to be approximately 1 in 100,000 births. This low rate leads to the disease often being classified as an ultra-rare disorder.
Obtaining precise global prevalence statistics is challenging due to underdiagnosis and the lack of comprehensive national registries for rare diseases. However, the overall prevalence in the general population remains extremely low. The carrier rate—the frequency of people who carry one copy of the mutated gene but are unaffected—in the non-Ashkenazi Jewish population is estimated to be about 1 in 439.
Understanding Autosomal Recessive Inheritance
Canavan Disease follows an autosomal recessive inheritance pattern, meaning the disease only manifests if a child inherits two copies of the mutated ASPA gene, one from each parent. Individuals who inherit only one copy are known as carriers; they are typically healthy and show no symptoms.
For two parents who are both asymptomatic carriers, the genetic risk for each pregnancy follows specific probabilities. There is a 25% chance the child will be affected by Canavan Disease. There is a 50% chance the child will become a healthy carrier, and a 25% chance the child will be neither affected nor a carrier. This mechanism allows the disease to remain hidden in a family line for generations until two carriers reproduce.
Targeted Screening for High-Risk Populations
While Canavan Disease occurs in all ethnic groups, the risk is significantly concentrated within certain populations due to historical factors. The highest incidence and carrier frequency are found in people of Ashkenazi Jewish descent. Within this population, the carrier rate is substantially higher, estimated to be between 1 in 36 and 1 in 60 individuals.
This increased frequency is attributed to the “founder effect,” which occurs when a small, isolated group expands over time, concentrating specific gene mutations. In this population, two specific mutations (E285A and Y231X) account for the vast majority of Canavan Disease cases.
The elevated risk has led to recommendations for targeted genetic carrier screening. Medical organizations advise that individuals of Ashkenazi Jewish descent planning a pregnancy consider screening to determine their carrier status. Identifying carrier status allows prospective parents to understand their risk and explore reproductive options.