Metachromatic Leukodystrophy: Symptoms, Causes And Treatment
Metachromatic leukodystrophy is an inherited disease and neurodegenerative that affects the white matter of the nervous system and is caused by an enzyme deficiency. This disorder causes serious effects at the neurocognitive level and on motor functions.
In this article we explain what this disease consists of and what its main characteristics are, its variants, the causes that cause it, its symptoms and the indicated treatment.
Metachromatic leukodystrophy: definition and characteristics
Metachromatic leukodystrophy is a rare inherited disorder, belonging to the group of lysosomal storage diseases, which is characterized by the accumulation of sulfatides in cells, especially in the nervous system This accumulation causes the progressive destruction of the white matter of the brain, made up of nerve fibers covered with myelin.
Myelin is a substance that covers the axons of nerve cells and its function is to increase the speed of transmission of nerve impulses. Its deterioration or destruction causes devastating effects on the patient’s cognitive functions and motor skills.
The main characteristic of leukodystrophies that belong to the group of lysosomal diseases, such as metachromatic leukodystrophy, is improper functioning of lysosome enzymes a cellular structure that contains numerous enzymes and whose function is to degrade and recycle intracellular material (of external and internal origin), in a process known as cellular digestion.
This disease can have its onset in childhood, adolescence or adulthood, and is transmitted hereditarily with an autosomal recessive pattern; That is, the person has to inherit two copies of the genetic mutation (one from each parent) to suffer from the disease. The incidence of metachromatic leukodystrophy at birth is estimated at 1 case per 45,000 children, and represents around 20% of all leukodystrophies.
The causes that cause metachromatic leukodystrophy are genetic; specific, Various mutations in the ARSA and PSAP genes appear to be responsible for the development of a deficiency of the enzyme arylsulfatase A (ARSA) which is responsible for breaking down sulfatides and other fats.
In rare cases, a deficiency of the activating protein saposin B (Sap B), which helps the enzyme ARSA break down these fats, could also be another possible cause of the disease. The accumulation of sulfatides in cells would be due to a malfunction of the joint work carried out by ARSA and Sap B when degrading these fatty compounds.
Types (and symptoms of each of them)
There are three types of metachromatic leukodystrophy, which are classified based on the age of onset of the disease, each with its distinctive symptoms. Let’s see what they are:
1. Late infantile form
This form of metachromatic leukodystrophy It is the most common and represents around 50-60% of cases It usually originates in the first two years of life and children, after a period of relative normality, lose the acquired skills and suffer from mobility problems (abnormal or erratic movements) and muscle weakness (problems when walking or crawling).
These children are often diagnosed with cerebral palsy due to mobility impairments As the disease progresses, muscle tone decreases until reaching a state of absolute rigidity, speech problems become increasingly evident and difficulties appear in fine motor skills.
Ultimately, the child loses his or her ability to think, understand, and interact with other people. The mortality rate is high and children do not usually survive past infancy.
This form of metachromatic leukodystrophy is the second most common (around 20-30% of cases). It usually begins between the ages of 2 or 3 and adolescence. The first symptoms of the disease have to do with problems with fine motor skills and concentration Behavioral alterations may also occur during the academic year.
These children may also have difficulty interacting with their peers and are sometimes suspected of having a possible diagnosis of schizophrenia or depression. In the early stages, they can barely move, coordinate, walk, or develop speech properly.
As symptoms progress, other neurological signs appear such as involuntary flexion, tremors, muscle rigidity with eventual loss of gait The progression of the disease is slower than that which occurs in the late childhood variant and affected children can survive for about 20 years after diagnosis.
3. Adult form
The adult form is the least common variant of metachromatic leukodystrophy (15-20% of cases). The first symptoms appear during adolescence or later and are reflected in poor school or work performance, with a progressive decline in cognitive abilities and behavioral problems The affected person may also suffer psychiatric symptoms such as delusions or hallucinations.
Additionally, patients experience motor clumsiness and may become incontinent. Paralysis of the arms and legs also occurs, which develops progressively. Occasionally, seizures can also occur. In the final stages of the disease, affected individuals may reach a vegetative state.
With everything, If you suffer from this variant you can survive for 20 or 30 years after diagnosis During this time there may be some periods of relative stability, compared to other periods of greater instability.
Although still There is no definitive cure for metachromatic leukodystrophy the usual treatments for this disease include:
1. Symptomatic and supportive treatment
It is based on antiepileptic drugs, muscle relaxants, physical therapy to improve muscle function and mobility, cognitive stimulation and support for family members to anticipate future decisions about the acquisition of technical aids (walkers, wheelchairs, feeding tubes, etc.).
2. Hematopoietic stem cell or bone marrow transplant
Here use is made of healthy stem cells that are obtained from a donor’s blood or bone marrow and injected into the patient This procedure is not recommended in the late infantile variant, but can be potentially beneficial in patients with the juvenile and adult form, especially in the early stages of the disease.
3. Enzyme replacement therapy
Although this therapy is still under investigation and clinical trials are underway, animal studies suggest that it could reduce sulfatide accumulation and lead to functional improvement in the patient.
4. Gene therapy
It consists of replacing defective genes with healthy copies It may be a treatment in the future and work and research is being done for it
5. Injection of adeno-associated viral vectors
This method consists of injecting a genetically modified virus that contains a normal copy of the ARSA gene into the brain, so that it can “infect” the cells and incorporate the gene into them. Thus, theoretically, enzyme levels would be restored. It has been successful in animal models and clinical trials are being carried out in several countries.
