Canavan disease is a rare inherited genetic condition that presents neurological disorder in infants. Although at birth the affected infants appear normal, they tend to develop symptoms associated with this condition between 3-6 months of age. Canavan disease occurs with the lack of a certain type of enzyme that results in the deterioration of the white matter (myelin) in the brain affecting the normal nerve signal process. The white matter is composed of nerve fibers which are coated with the lipids and proteins called myelin that help with the transmission of nerve signals. The affected children mostly develop serious complications by the age of 10. As this is a progressive condition, these affected individuals die within the first two decades of their life. The prevalence of this disease is not exactly known, although it appears to be common in the population of the Ashkenazi Jewish heritage (eastern and central European). It is estimated that the disorder affects 1 in 6,400 to 13,500 individuals of Ashkenazi Jewish population.
Causes
This disease is inherited in an autosomal recessive pattern meaning both the copies of the gene in each cell are defective. The parents of individuals affected with this condition each carry one copy of the defective gene but may not exhibit any signs and symptoms associated with this disease. The gene responsible for this disease is identified as ASPA which delivers the information necessary to produce an enzyme known as aspartoacylase. The defect in the gene prevents the normal breakdown of a compound called N-acetyl-aspartic acid (NAA). The accumulation of NAA compound in the brain affects the myelin sheaths and disrupts the brain development.
Symptoms
The progression and the severity of the symptoms vary among the affected individuals. Generally, the disease may onset at the age of 3 to 6 months exhibiting problems in their normal development. The symptoms consist of abnormally large head (macrocephaly) and poor muscle tone (hypotonia). The other problems include not developing the motor skills with the inability to control head movements, turning over, unable to sit without requiring support and not walking independently. They also have difficulties with feeding, swallowing, irritability, seizures, nasal regurgitation, deterioration of the nerves in the eyes affecting the vision and sleep disturbances. Mental retardation also becomes evident in the infancy and some cases may have hearing problems.
Diagnosis
The diagnosis of this disease includes the CT or MRI scan which identifies the deterioration of the white matter in the brain. The additional tests can include the urine, blood or cerebrospinal fluid test to evaluate the level of N-acetyl-L-aspartate (NAA) fluids and the increased level can indicate the deficiency of the enzyme aspartoacylase. The genetic testing can identify the mutation in the gene that causes this disorder. The prenatal genetic screening is possible, particularly when the prevalence of this disease is suspected in the family.
Treatment
There is no cure for canavan disease. The treatment usually focuses on the specific symptoms that are evident in each of the cases. The supportive care for these affected individuals can help with the discomfort. If swallowing difficulties are present, the feeding tubes may be beneficial in ensuring they meet the nutritional needs. In the case of seizures, the anticonvulsant medications can treat the condition. In some cases, genetic counseling may be beneficial for the individual’s families.
References
https://rarediseases.org/rare-diseases/canavan-disease/
https://ghr.nlm.nih.gov/condition/canavan-disease#genes
http://www.canavanfoundation.org/how_canavan_disease_is_inherited
http://ulf.org/canavan-disease
