Kanavan's disease (spongiozny degeneration) — a genetic neurodegenerate disease which cornerstone the lack of enzyme of an aspartoatsilaza leading to a demiyelinization of nervous fibers of a brain is. Kanavan's disease is shown at early children's age by violations of motility and development of the child, difficulties at meal, muscular hypotonia, a makrotsefaliya, epileptic seizures, a blindness. Kanavan's disease according to the analysis of urine on N-acetyl-asparaginovuyu acid is diagnosed. Effective therapy of a disease is not found yet. Attempts to treat Kanavan's disease by means of metabolic therapy and by use of the gene technologies capable to replace a pathological aberration with a healthy gene are made.
Kanavan's disease was described by Mirtel Kanavan in 1931. And in 1991 Ruben Matalon allocated the gene which is responsible for this disease. Several years later the test allowing to diagnose Kanavan's disease even during conducting pregnancy began to be applied. Kanavan's disease occurs at people of any nationality. However most often Ashkenazi's Jews are ill it. Among them the carrier of the gene aberration coding Kanavan's disease is 1 of 40 people.
The modern neurology carries Kanavan's disease to so-called leykodistrofiya — genetically caused degenerate diseases of nervous system which cornerstone violation of metabolism of lipids is. Most often violations concern a myelin which for 70-75% consists of lipids. Disintegration of a myelin leads to destruction of a myelin cover of nervous trunks and secondary death of neurons. The progressing demiyelinization which is the cornerstone of a disease does Kanavan's disease and other leykodistrofiya similar to demiyeliniziruyushchy diseases of a brain which have the acquired character (the multiple sclerosis disseminated by encephalomyelitis, poliradikulonevropatiy Giyena-Barra, Devik's disease).
Causes of a disease of Kanavan
Kanavan's disease is connected with a genetic disorder in ASPA genome located in the 17th chromosome. Owing to this genetic aberration synthesis of the enzyme of an aspartoatsilaza splitting N-acetyl-asparaginovuyu the acid which is formed in the course of activity of cells of the central nervous system is reduced. Pathologically high level of this acid leads to damage of a myelin cover of nervous fibers of a brain. The myelin cover carries out a role of the peculiar insulator which is not allowing a nervous impulse to pass from one nervous fiber to another. Thus, the myelin cover promotes exact and bystry carrying out nervous impulses. At its destruction this process is broken, as is an immediate cause of clinical displays of a disease of Kanavan.
Kanavan's disease is transmitted on autosomno-recessive type of inheritance. It means that the probability of the birth at them of the child having Kanavan's disease is equal in a situation when both parents are carriers of a pathological gene, to 25%.
Symptoms of a disease of Kanavan
At the birth the child having Kanavan's disease differs in nothing from healthy newborns. Symptoms of a disease begin to be shown a month later, and is more often during the period of 3 months before half a year. The delay in development, slowness of movements, loss of already acquired movement skills, decrease in a muscular tone is noted. The arising difficulties when swallowing cause essential difficulties when feeding the child. Approximately by 4th month of life to become increase in the head (makrotsefaliya) is noticeable. Progressing of a disease of Kanavan is followed by developing of epileptic seizures. Demiyelinization and an atrophy of an optic nerve leads to development of a blindness.
Diagnosis of a disease of Kanavan
Kanavan's disease represents for the neurologist certain difficulties in diagnostics as demiyeliniziruyushchy process is observed at a number of both congenital, and acquired diseases. Standard methods of primary neurologic inspection, such as electroencephalography and ultrasonografiya do not reveal specific changes. Carrying out MRT of a brain is complicated because of too early age of patients. The most reliable method allowing to diagnose Kanavan's disease is the analysis of urine on N-acetyl-asparaginovuyu acid.
Geneticists recommend to all Jewish people to undergo when planning pregnancy screening on existence of the gene mutation defining Kanavan's disease. Screening should be undergone also to those people in whose family the case of this disease was observed. The methods of prenatal diagnostics allowing to establish Kanavan's disease till the child's birth are developed. The indication to carrying out a similar research is the established carriage of a pathological gene at both parents. As material for a research on Kanavan's disease serve the amniotic liquid received as a result of amniocentesis or the vorsina of a horion taken during a transabdominal or transtservikalny biopsy of a horion.
Treatment of a disease of Kanavan
Now there is no technique by means of which it would be possible to treat effectively Kanavan's disease. It is possible to slow down development of a disease at application of metabolic therapy. It consists in intake of the whole complex of medicines: citrate of lithium, acetate of calcium, suktsinat of sodium.
The most optimistical among modern experimental developments in the field of treatment of a disease of Kanavan is gene therapy. Development of a method of gene therapy capable it is considerable to prolong life to the patients having Kanavan's disease, it is carried out to New Jersey (USA). Her idea consists in cloning and introduction in an organism of a healthy gene capable to replace a pathological gene. Carriers of the new artificially synthesized gene are not pathogenic adenoassotsiirovanny viruses which are found in solution in a brain through 6 catheters established in its various areas. Experimental treatment there underwent 13 children. Their subsequent inspection showed that as a result of gene therapy Kanavan's disease slowed down the progressing, there was a decrease toxic N-acetyl-asparaginovoy of acid and increase the maintenance of a myelin.
Forecast of a disease of Kanavan
Unfortunately, Kanavan's disease leads to a lethal outcome at infantile age. In rare instances patients live up to age of 10 years.