Canavan’s disease is a genetic autosomal recessive neurodegenerative disease, also known as Canavan—Van Bogert-Bertrand disease. This is spongiose degeneration of the white matter of the brain, spongiose infant degeneration, in which there is a progressive lesion of nerve cells of the brain. An autosomal recessive type of heredity means that a child born to parents who carry this disease has a high risk of getting sick (approximately 25%). This disease is rare, but at the same time one of the most common in children, associated with a violation of the brain. It belongs to a group of genetic diseases called leukodystrophy.
The content of the article:
Causes of Canavan’s disease
Symptoms of Canavan’s disease
Diagnosis of Canavan’s disease
Treatment of Canavan’s disease
Prognosis of Canavan’s disease
Canavan’s disease
The disease manifests itself in early childhood, is more common among the Jewish population of Ashkenazi.
Causes of Canavan’s disease
Canavan’s disease is caused by the mutated ASPA gene, which synthesizes the enzyme aspartoacylase and is located on the seventeenth chromosome.
In the brain, acetylaspartic acid is formed in high concentrations from aspartic acid and is present there in the same way as glutamic acid.
The role and significance of this acid is not fully defined, but it is known that a lack of aspartoacillase leads to the occurrence of Canavan’s disease. Then this acid is excreted from the body with urine, increasing its concentration at times. A large amount of this acid appears in the blood and in the brain itself, especially in the white matter, where there is a sharp swelling of astrocytes.
In electronic diagnostics, mitochondrial deformation is detected. Progressive atrophic processes occur in the brain, as a result of which the cerebral ventricles increase in volume. The formation of the myelin sheath is disrupted (a special layer of fats covering nerve cells, as if isolating them, not allowing the nerve impulse to pass from one nerve fiber to another).
Symptoms of Canavan’s disease
Canavan’s disease may not initially manifest itself in any way. Only a month or three months after the birth of the child is it likely to make a final diagnosis.
Symptoms of Canavan ‘s disease include:
development of muscular hypotension (the child does not hold his head);
increased drowsiness;
decreased neck muscle tone and increased limb muscle tone;
joint stiffness;
the presence of seizures;
chaotic movement of the eyeballs;
epileptic seizures;
food reflux, impaired swallowing function;
limb paralysis;
enlargement of the brain and the formation of cavities in it;
optic nerve atrophy — blindness (by the age of two);
macrocephaly — enlargement of the head due to fluid accumulation;
severe lag in development.
The symptoms of Canavan’s disease progress rapidly, so the life expectancy of patients is shortened. The final stage of the disease development is characterized by immobilization of the patient, difficulty breathing and blood circulation.
Diagnosis of Canavan’s disease
Diagnosis of Canavan’s disease is a complex process, because similar symptoms are observed among other congenital or acquired diseases.
To determine Canavan’s disease or confirm the diagnosis, a thorough diagnosis is carried out, including:
blood analysis and organic urine analysis for acidity;
CT;
MRI;
a genetic test for gene mutations.
A urine and blood test immediately reveals a high concentration of acetylaspartic acid. The process of MRI is difficult, since the age of patients is very small, so inaccuracies in diagnosis may occur. MRI helps to detect spongy degeneration of nerve fibers of the myelin fat layer, as well as swelling of astrocytes and deformation (elongation) of mitochondria. The concentration of aspartoacylase in cutaneous fibroblasts in carriers of Canavan’s disease is approximately two times lower than normal. Magnetic resonance spectroscopy shows the highest concentration of acetylaspartic acid in the brain. Especially important is the biochemical analysis of blood and urine, which give the conclusion of the diagnosis, play a crucial role.
There are diagnostic methods that can detect this disease of a child in the womb (perinatal diagnosis). To do this, it is necessary to establish, first of all, a deformed pathological gene in both parents. To confirm or refute the diagnosis, an amniocentesis is performed to obtain amniotic fluid. Transabdominal or transcervical chorionic biopsy is also practiced to obtain chorionic villi.
Geneticists recommend that people with a family history of this disease, when planning a family, undergo a thorough examination — screening to identify a modified gene.
Treatment of Canavan’s disease
Effective and standard methods, as well as drugs for the treatment of Canavan’s disease, do not exist today. The course of treatment is purely individual and has a supportive character. The disease is considered fatal. Patients often die before the age of two, in some cases the life expectancy can be up to ten years, in rare cases up to twenty. With the help of metabolic therapy, it is possible to slow down the development of the disease. Taking a number of medications (calcium acetate, lithium citrate, sodium succinate, milidiamox) will be able to stop the progression of the disease, but it will not be able to stop it. All the drugs needed for treatment are expensive.
Experimental treatment
Experiments of lithium nitrate-based medial therapy (conducted in laboratory conditions on animal organisms) gave encouraging results of the suspension of the disease. This became the basis for the continuation of experimental lithium-based treatment.
At the experimental level, various methods of treatment are being investigated, in particular, gene therapy. For example, liposomes with the aspartoacialase gene were injected into the ventricles of the patient’s brain through several catheters as a solution. The procedure was carried out as an experimental treatment with the participation of more than a dozen sick children and did not lead to the desired result — complete elimination of the disease, although it is considered the most successful, since with its help it was possible to suspend the development of the disease.
Encouraging results were obtained by experiments using triacetin, which is broken down to acetate for better assimilation by the body.
Prognosis of Canavan’s disease
Canavan’s disease leads to the death of a patient conceived in the first two years of development if it is not treated in time. The use of gene therapy can prolong the patient’s life for several years. Cases of termination of the disease for a short time due to treatment with gene therapy have been reported.
