Canavan disease is the most prevalent degenerative neurological disorder in childhood. It is a serious, often fatal, genetic alteration that causes the deterioration of myelin, a substance that surrounds the axons of neurons to facilitate the transmission of nerve impulses, so they do not propagate properly.
This disorder is included in the group of leukodystrophies, diseases associated with alterations in the development and maintenance of myelin sheaths. Other diseases belonging to this group are Alexander’s, Krabbe’s, Pelizaeus-Merzbacher’s and adrenoleukodystrophy.
They have differentiated two variants of Canavan disease: neonatal/infantile and juvenile. While the former involves more severe symptoms and is detected early, the juvenile subtype is considered a mild variant in which only modest delays in motor and verbal development may appear; It also has a better prognosis.
Many of the girls and boys with the severe variant of Canavan disease They die before turning 10 years old. Others manage to survive until approximately 20 years of age, while life expectancy does not seem to be reduced in mild cases.
This disease is much more common in people who have a genetic heritage of Ashkenazi Jewish origin, from central and eastern Europe. This population group has been widely studied by the medical community due to its high degree of endogamy.
Although the first symptoms of Canavan disease They commonly appear during the first year of life the rapid and progressive degeneration of the cerebral white matter causes more severe alterations to arise, mainly related to the loss of motor and sensory abilities.
The symptoms and signs of this disorder can vary greatly depending on whether we are talking about the infantile or juvenile variant, as well as the particular characteristics of each case. Some of the most common are the following:
Causes of this disease
Canavan’s disease It occurs as a result of abnormalities in the ASPA gene, which contains the information necessary to synthesize the enzyme aspartoacylase. This compound allows the metabolization of the amino acid N-acetyl-L-aspartate, probably involved in brain homeostasis and in the synthesis of oligodendrocytes, which form myelin.
In people who suffer from this disease, mutations in the ASPA gene prevent this amino acid from being processed properly. By focusing excessively on the nervous system interferes with the formation of myelin sheaths and causes them to deteriorate progressively. Consequently, neuronal transmission is also affected.
This alteration is transmitted through an autosomal recessive inheritance mechanism, which means that a baby has a 25% chance of developing the disease if both its mother and father are carriers of the defective gene.
Treatment and management
It is currently not entirely clear whether there are effective methods to treat the genetic alterations that cause Canavan disease. Because of this Treatment is basically symptomatic and supportive and it depends on the specific manifestations of each case.
Swallowing difficulties can be very problematic; In some cases it is necessary to apply feeding and hydration tubes to ensure patient survival. Respiratory care and prevention of infectious diseases are also particularly important.
Physical therapy is very useful to enhance motor and postural abilities of boys and girls with Canavan disease. It can also relieve contractures, which are very common due to changes in muscle tone.
Interventions are more effective if they begin to be applied at an early stage of the development of the affected children, since in this way it is possible to minimize to a certain extent the appearance or progress of some of the symptoms, such as muscle symptoms and those related to the communication.
Currently there are treatments in the experimental phase that focus on genetic alterations and metabolic associated with defects in the ASPA gene. These therapeutic approaches require further investigation, although they are providing promising data for the future management of Canavan disease.
