Canavan disease: symptoms, causes and treatment

Inherited defects in the ASPA gene alter the myelin sheaths, which significantly affects the functioning of the nervous system.

In this article we will describe Canavan disease symptoms, causes and treatment, the name by which this alteration of neural transmission is known.

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What is Canavan disease?

Canavan disease is the most prevalent degenerative neurological disorder in childhood. It is a serious, often fatal genetic disorder that causes the deterioration of myelin, a substance that surrounds the axons of the neurons to facilitate the transmission of nerve impulses, so they do not propagate properly.

This disorder is included within 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.

have differentiated two variants of Canavan disease: neonatal/infantile and juvenile

. While the former has more severe symptoms and is detected early, the juvenile subtype is considered a mild variant in which only modest delays in motor development and verbal; it also has a better prognosis.

A good part of the girls and boys with the severe variant of Canavan disease die before the age of 10. Others manage to survive until approximately 20 years, 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, Central and Eastern European origin. This population group has been extensively studied by the medical community due to its high degree of inbreeding.

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Main symptoms and signs

Although the first symptoms of Canavan disease commonly appear during the first year of life, the rapid and progressive degeneration of the cerebral white matter leads to the appearance of more severe alterations, 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 the juvenile variant, as well as the particular characteristics of each case. Some of the most common are the following:

• Severe alterations in motor development
• inability to speak
• Lack of development of the ability to crawl, walk and sit
• Increased muscle tone (hypertonia, rigidity) or decreased (hypotonia, flaccidity)
• Increased head size (macrocephaly)
• head motor control deficit
• Reduced visual responsiveness
• Difficulties swallowing and eating
• Appearance of epileptic seizures
• development of paralysis
• Progressive blindness and deafness
• Trouble falling or staying asleep
• Irritability

Causes of this disease

Canavan's disease occurs as a consequence 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 said amino acid from being processed properly. By concentrating excessively on the nervous system interferes with the formation of myelin sheaths and causes them to deteriorate progressively. Consequently, neural transmission is also affected.

This alteration is transmitted through an autosomal recessive inheritance mechanism, which implies that a baby has 25% chance of developing the disease if both her mother and her father carry the gene defective.

Treatment and management

At present it is 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 concrete manifestations of each case.

Difficulties swallowing can be very problematic; in some cases it is necessary to apply feeding and hydration tubes to ensure the survival of the patient. Respiratory care and the prevention of infectious diseases are also particularly important.

Physical therapy is very useful to enhance motor and postural abilities of children with Canavan disease. It can also alleviate contractures, which are very common due to changes in muscle tone.

The 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 some degree the appearance or progression of some of the symptoms, such as muscular and communication.

Currently there are experimental phase treatments that focus on genetic alterationsand 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.