Hereditary defects in the ASPA gene alter the myelin sheath, which has a significant impact on the functioning of the nervous system.

In this article we will describe the symptoms, causes and treatment of Canavan disease , the name of this neural transmission disorder.

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 neurons to facilitate the transmission of nerve impulses, so that these do not spread 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 disease, Krabbe disease, Pelizaeus-Merzbacher disease and adrenoleukodystrophy.

Two variants of Canavan disease have been differentiated : neonatal/infant and juvenile . While the first one 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 children with severe variant Canavan disease die before their 10th birthday . Others manage to survive until about 20 years of age, while life expectancy does not seem to be reduced in mild cases.

This disease is much more frequent in people who have a genetic heritage of Ashkenazi Jewish origin, from central and eastern Europe. This population group has been studied extensively by the medical community because of their high degree of inbreeding.

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 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 disturbances in motor development
  • Inability to speak
  • Lack of development of the ability to crawl, walk and sit
  • Increased (hypertonia, rigidity) or decreased (hypotonia, flaccidity) muscle tone
  • Increased head size (macrocephaly)
  • Deficits in motor control of the head
  • Reduction of visual responsiveness
  • Swallowing and eating difficulties
  • Occurrence of epileptic seizures
  • Development of paralysis
  • Progressive blindness and deafness
  • Problems falling or staying asleep
  • Irritability

Causes of this disease

Canavan disease occurs as a result of abnormalities in the ASPA gene , which contains the information needed 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 with this disease, mutations in the ASPA gene prevent the amino acid from being processed properly. By concentrating excessively on the nervous system it interferes with the formation of the myelin sheaths and causes them to progressively deteriorate. Consequently, neuronal transmission is also affected.

This disorder 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 carry the defective gene.

Treatment and handling

At present it is not entirely clear whether there are effective methods for treating the genetic disorders that cause Canavan disease. Because of this the treatment is basically symptomatic and supportive and 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 the patient’s survival. Airway care and prevention of infectious diseases are also particularly important.

Physical therapy is very useful to enhance the motor and postural capacities of children with Canavan disease. It can also relieve contractures, which are very frequent due to alterations in muscle tone.

Interventions are most effective if they are started early in the development of affected children, as this can minimise to some extent the occurrence or progression of some of the symptoms, such as muscular and communication-related ones.

There are currently treatments in the experimental phase that focus on genetic and metabolic alterations associated with defects in the ASPA gene. These therapeutic approaches require further research, although they are providing promising data for the future management of Canavan disease.