Canavan disease (spongiose infant degeneration) is a genetic neurodegenerative disease based on a lack of the enzyme aspartoacylase, which leads to demyelination of the nerve fibers of the brain. Disease manifests itself in early childhood with impaired motor skills and child development, difficulty eating, muscle hypotension, macrocephaly, epileptic seizures, blindness. Pathology is diagnosed by urine analysis for N-acetyl-aspartic acid. Effective therapy of the disease has not yet been found. Attempts are being made to treat with the help of metabolic therapy and through the use of gene technologies that can replace pathological aberration with a healthy gene.
ICD 10
E75.2 Other sphingolipidoses
General information
Canavan disease was described by Myrtel Canavan in 1931. And in 1991, Ruben Matalon isolated the gene responsible for this disease. A few years later, a test began to be used to diagnose Canavan disease even during pregnancy. Disease occurs in people of any nationality. However, Ashkenazi Jews most often suffer from it. Among them, 1 out of 40 people is a carrier of the gene aberration encoding Canavan disease.
Modern neurology refers Canavan disease to the so—called leukodystrophy – genetically determined degenerative diseases of the nervous system, which are based on a violation of lipid metabolism. Most often, violations concern myelin, which is 70-75% composed of lipids. The breakdown of myelin leads to the destruction of the myelin sheath of nerve trunks and secondary death of neurons. The progressive demyelination underlying the disease makes Canavan disease and other leukodystrophy similar to demyelinating brain diseases that have an acquired character (multiple sclerosis, multiple encephalomyelitis, Guillain-Barre polyradiculoneuropathy, Devic’s disease).
Causes
Canavan disease is associated with a genetic disorder in the ASPA genome located on chromosome 17. As a result of this genetic aberration, the synthesis of the enzyme aspartoacylase, which cleaves N-acetyl-aspartic acid formed during the vital activity of cells of the central nervous system, is reduced. Pathologically high levels of this acid lead to damage to the myelin sheath of the nerve fibers of the brain. The myelin sheath acts as a kind of insulator that does not allow the nerve impulse to pass from one nerve fiber to another. Thus, the myelin sheath contributes to the accurate and rapid conduction of nerve impulses. When it is destroyed, this process is disrupted, which is the direct cause of the clinical manifestations.
Canavan disease is transmitted by an autosomal recessive type of inheritance. This means that in a situation where both parents are carriers of a pathological gene, the probability of their having a child with Canavan disease is 25%.
Symptoms
At birth, a child with Canavan disease is no different from healthy newborns. Symptoms of the disease begin to appear after a month, and more often in the period from 3 months to six months. There is a delay in development, slowness of movements, loss of already acquired motor skills, a decrease in muscle tone. The difficulties that arise when swallowing cause significant difficulties when feeding a child. By about the 4th month of life, an increase in the head (macrocephaly) becomes noticeable. The progression is accompanied by the occurrence of epileptic seizures. Demyelination and atrophy of the optic nerve leads to the development of blindness.
Diagnostics
Canavan disease presents certain difficulties for a neurologist in diagnosis, since the demyelinating process is observed in a number of both congenital and acquired diseases. Standard methods of primary neurological examination, such as electroencephalography and ultrasonography do not reveal specific changes. MRI of the brain is difficult due to the too young age of patients. The most reliable method for diagnosing Canavan disease is a urine test for N-acetyl-aspartic acid.
Geneticists recommend that all persons of Jewish nationality, when planning a pregnancy, undergo screening for the presence of a gene mutation that determines Canavan disease. Screening should also be carried out for those people in whose family a case of this disease has been observed. Methods of prenatal diagnostics have been developed to establish Canavan disease even before the birth of a child. The indication for conducting such a study is the established carrier of a pathological gene in both parents. The amniotic fluid obtained as a result of amniocentesis or chorionic villi taken during transabdominal or transcervical chorionic biopsy serve as the material for research on Canavan disease.
Treatment
Currently, there is no method by which it would be possible to effectively treat Canavan disease. It is possible to slow down the development of the disease with the use of metabolic therapy. It consists in ingestion of a whole complex of medications: lithium citrate, calcium acetate, sodium succinate.
The most optimistic among modern experimental developments in the treatment of Canavan disease is gene therapy. The development of a gene therapy method that can significantly prolong the life of patients is being carried out in New Jersey (USA). Her idea is to clone and introduce into the body a healthy gene that can replace a pathological gene. Carriers of the new artificially synthesized gene are non-pathogenic adenoassociated viruses, which are found in solution in the brain through 6 catheters installed in its various areas. 13 children underwent experimental treatment. Their subsequent examination showed that as a result of gene therapy, Canavan disease slowed its progression, there was a decrease in toxic N-acetyl-aspartic acid and an increase in myelin content.
Forecast
Unfortunately, Canavan disease leads to a fatal outcome even in infancy. In rare cases, patients live to the age of 10 years.
