Canavan disease: symptoms, causes and treatment

This is the most common neurodegenerative disorder in children and can be fatal.

Inherited defects in the ASPA gene alter the myelin sheaths, 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 given to CanavanThis is the name given to this alteration of neural transmission.

What is Canavan disease?

The disease of Canavan is the most prevalent degenerative neurological disorder in childhood.. It is a serious genetic disorder, often fatal, which causes the deterioration of myelin, a substance that surrounds the axons of neurons to facilitate the transmission of nerve impulses, so they 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's disease, Pelizaeus-Merzbacher disease and adrenoleukodystrophy.

Two variants of 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 occur; it also has a better prognosis.

Most children with the severe variant of Canavan disease die before the age of 10. die before their 10th birthday. Others manage to survive until they are about 20 years old, while life expectancy does not seem to be reduced in mild cases.

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

Main symptoms and signs

Although the first symptoms of Canavan disease commonly appear in the first year of life commonly appear during the first year of lifeThe rapid and progressive degeneration of the cerebral white matter causes more severe alterations to emerge, 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:

• Severe disturbances in motor development
• Inability to speak
• Lack of development of the ability to crawl, walk and sit up.
• Increased (hypertonia, stiffness) or decreased (hypotonia, flaccidity) Muscle tone
• Increased head size (macrocephaly)
• Deficits in motor control of the head
• Reduced visual responsiveness
• Swallowing and eating difficulties
• Development of epileptic seizures
• Development of paralysis
• Progressive blindness and deafness
• Trouble falling or staying asleep
• Irritability

Causes of this disease

Canavan disease is caused by 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 with this disease, mutations in the ASPA gene prevent this amino acid from being processed properly. When it concentrates in excess in the nervous system interferes with the formation of the myelin sheaths and causes them to deteriorate progressively. Consequently, neuronal transmission is also affected.

This alteration is transmitted by 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

At present it is not entirely clear whether there are effective methods to treat the genetic alterations that cause Canavan disease. Because of this the treatment is basically symptomatic and supportive and depends on the and depends on the specific manifestations of each case.

Swallowing difficulties can be very problematic; in some cases feeding and hydration tubes are necessary to ensure the survival of the patient. Airway care and prevention of infectious diseases are also particularly important.

Physical therapy is very useful to enhance the motor and postural abilities of children with the disease. children with Canavan disease. It can also alleviate 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 minimize to some degree the onset or progression of some of the symptoms, such as muscular and communication-related symptoms.

There are currently experimental treatments targeting genetic and metabolic alterations are currently available 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.