Hereditary 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 symptoms, causes and treatment of Canavan disease, Name by which this alteration in neuronal transmission is known.
What is Canavan disease?
Canavan disease is the most common degenerative neurological disorder in childhood. It is a serious, often fatal, genetic disease that causes the breakdown of myelin, a substance that surrounds the axons of neurons to facilitate the transmission of nerve impulses so that 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, Krabbe, Pelizaeus-Merzbacher and adrenoleukodystrophy.
They differentiated themselves two variants of Canavan disease: neonatal / infantile and juvenile. While the former carries 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 can appear; it also has a better prognosis.
Many girls and boys with severe variant Canavan disease they die before they are 10 years old. Others manage to survive for up to around 20 years, while life expectancy does not appear to be reduced in mild cases.
This disease is much more common in people who have a genetic heritage of Ashkenazi Jewish origin, Central and Eastern Europe. This population group has been studied extensively by the medical community due to its high degree of inbreeding.
Main symptoms and signs
Although the first symptoms of Canavan disease they usually 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 capacities.
Symptoms and signs of this disorder can vary widely depending on whether it is the childish or juvenile variant, as well as the particular characteristics of each case. Some of the most common are:
- Severe changes in motor development
- Inability to speak
- Lack of development of the ability to crawl, walk and sit
- Increase in muscle tone (hypertension, stiffness) or decrease (hypotonia, sagging)
- Increase in head size (macrocephaly)
- Impaired motor control of the head
- Reduced visual responsiveness
- Difficulty swallowing and eating
- Onset of epileptic seizures
- Development of paralysis
- Progressive blindness and deafness
- Problems reconciling or maintaining sleep
The causes of this disease
Canavan 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 metabolism of the amino acid N-acetyl-L-aspartate, probably involved in cerebral 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 transforming properly. Focusing excessively on the nervous system interferes with the formation of myelin sheaths and causes them to deteriorate gradually. Therefore, neuronal transmission is also affected.
This alteration is transmitted by an autosomal recessive transmission mechanism, which means that a baby has a 25% chance of developing the disease if both his mother and father carry the defective gene.
Processing and handling
It is currently not entirely clear whether there are effective methods of treating the genetic alterations that cause Canavan disease. Because of that treatment is mainly symptomatic and supportive and depends on the specific manifestations of each case.
Difficulties in swallowing can be very problematic; in some cases, feeding and hydration tubes must be applied to ensure patient survival. Respiratory care and prevention of infectious diseases are also particularly important.
Physiotherapy is very helpful in improving motor and postural abilities boys and girls with Canavan disease. It can also relieve contractures, which are very common due to changes in muscle tone.
Interventions are most effective if they are applied at an early stage in the development of affected children, because in this way it is possible to minimize to some extent the appearance or progression of some of the symptoms, such as muscle and related to communication.
They currently exist experimental phase treatments focused on genetic alterations and metabolic associated with defects in the ASPA gene. These therapeutic approaches require further research, although they provide promising data for the future management of Canavan disease.