Metachromatic Leukodystrophy Definition and Meaning

A deficiency of arylsulfatase A in the organism leads to metachromatic leukodystrophy. It is a genetic metabolic disease of the brain and occurs in recessive inheritance, characterized by numerous mutations and effects in the manifestation, so that there are different symptom designations as well as the differences in the course and in the genotype.

What is metachromatic leukodystrophy?

Metabolic diseases that mainly affect the central nervous system are referred to in medicine as lipid storage diseases, more precisely as sphingolipidoses. They belong to the group of lysosomal storage diseases, are inherited and often have defects in certain genes. Metachromatic leukodystophism also belongs to this group. See AbbreviationFinder for abbreviations related to Metachromatic Leukodystrophy.

Arylsulfatase A is an enzyme responsible for splitting off sulfate from sulfatides. This process takes place in the lysosomes of the cells. These are the cell organelles in both animal and plant cells that have biomembrane -enclosed vesicles in which the acidic pH is present. Lysosomes contain digestive enzymes and they break down biopolymers into monomers.

If this enzyme is not active or if its activity is reduced, fat-containing substances gradually form in the body cells and in the central nervous system. Glycosphingolipids can no longer be split off and lipids can no longer be turned into lysosomes. The sulfatide is therefore stored. This in turn leads to rapid breakdown of the myelin sheaths. The latter is the lipid-rich layer around the axons of nerve cells, and its breakdown triggers leukodystrophy.


The name for the disease is derived from the Greek and contains both the words “color”, “white”, “bad” and “nutrition”. In metachromatic leukodystrophy, there is degeneration of demyelination, i.e. the white matter. The nerve fibers lose their marrow and the myelin sheath, which protects the nerve cell or axon, is destroyed or damaged in the central nervous system.

Symptoms, Ailments & Signs

In the course of the disease, there are disturbances in the movement functions, which worsen more and more. Those affected also change in their mental abilities. The brain function is more and more degraded.

The earlier the disease begins, the better the prognosis can be. A common form occurs late infancy and is then referred to as Greenfield syndrome. Symptoms appear between one and two years of age, while development is initially undisturbed. Even if the child was already able to speak and move normally, problems with walking suddenly appear, resulting in frequent stumbling.

The ability to express yourself verbally also deteriorates at first. Dysarthria occurs, as well as breathing and swallowing difficulties, which are often associated with this problem.

Muscle weakness and loss of reflexes are the result, since it is a peripheral nerve disease that also shows signs of spastic paralysis after some time. Painful muscle tension and pathological reflexes are the first indication of a disorder of the central nervous system. Even swallowing itself becomes more and more difficult, even if the symptoms stabilize periodically.

Hearing and vision soon begin to deteriorate, and complete blindness may result. The affected child can no longer move independently and is dependent on care and help. Mental abilities decline and dementia develops.

After a few years, the Greenfield syndrome leads to death, which then occurs at the latest in the 8th year of life due to decerebration rigidity, i.e. due to body rigidity in a coma, in which the brainstem is interrupted. There is hyperextension of the limbs and trunk.

Diagnosis & disease progression

Another form of metachromatic leukodystrophy is Scholz syndrome. This juvenile form occurs mostly in children between the ages of four and twelve and is characterized by a slow decline in school performance and deviations from usual behavioral patterns. For example, the child begins to take refuge in daydreams more and more frequently.

Other disorders include abnormal posture, difficulty walking, tremors, vision and speech disorders, various seizures and urinary incontinence. Gallstones also form in the body, which leads to colic and inflammation of the gallbladder. The child quickly becomes in need of care.

If the course of the disease is adult, there are more psychological problems. This can lead to depression, but also to schizophrenia. The onset of the disease can be during puberty, but symptoms can also only become noticeable in old age. Personality changes, performance decreases, emotional instability increases.

The loss of motor and mental abilities can be gradual and progressive over decades. A multiple sulfatase deficiency exacerbates the symptoms. This leads to mucosulfatidosis, with the deposits and storage not only taking place in the central nervous system, but also in the spleen, liver, lymph nodes and skeleton.


In most cases, this disease leads to various types of paralysis. The patients also suffer from spastic symptoms and not infrequently from epileptic seizures. These are usually associated with severe pain, so that those affected also suffer from depression or irritability in their everyday lives.

Involuntary muscle twitching can occur and make everyday life more difficult. Young people and children can also experience bullying or teasing. Furthermore, patients often suffer from poor concentration and coordination disorders. Memory loss can also occur, so that the child’s development is significantly restricted by the disease.

It is not uncommon for those affected to depend on the help of other people or their parents in everyday life. Relatives or parents can also experience severe mental health problems or depression. There is no cure for this disease, so only the symptoms can be treated symptomatically.

Complications usually do not arise. The symptoms can be alleviated with the help of medication and therapy. Whether the disease will lead to a reduced life expectancy cannot generally be predicted universally.

When should you go to the doctor?

Disturbances and irregularities in mobility are signs of a health impairment that should be clarified by a doctor. If symptoms of the movement sequences increase, a doctor’s visit must be made. Unsteady gait, dizziness, an increased risk of accidents or the inability to coordinate normal movements must be examined and treated. If the child has developmental disabilities, problems with locomotion, or frequent stumbling, there is cause for concern. If, in direct comparison to children of the same age, the child learns to walk particularly late or is not sure in its movement sequences, the observations should be discussed with a doctor.

Difficulty breathing or swallowing are other signs of illness. If the respiratory disorder leads to an insufficient supply of oxygen to the organism, a life-threatening condition threatens. Therefore, if the skin is pale or blue, it is advisable to consult a doctor. If there is an impairment of the ability to speak or if the ability of the person concerned to express themselves is disturbed, the indications should be clarified by a doctor. A doctor is required in the case of existing or increasing weakness in muscle strength, pain when tensing the muscles or a loss of natural reflexes. Functional disorders of the sensory organs must also be examined and treated by a doctor. In the worst case, reduced vision or hearing can lead to blindness and deafness.

Treatment & Therapy

Therapy for metachromatic leukodystrophy is very limited. Rather, resort to palliative measures, primarily treating those manifestations that relieve pain and muscle spasms, prescribe physiotherapy for spastic attacks. Antiepileptic drugs are intended to reduce seizures, and a special diet or special nutrition is one of the prerequisites for treatment.

Longer-lasting freedom from symptoms could also be achieved by transplanting stem cells or bone marrow. However, this surgical intervention only has positive effects if it takes place in the pre-symptomatic stage. It is also not unproblematic and entails risks and side effects.

Scientific experiments are still being carried out on tissue cultures and animals in order to clarify the pathogenesis and to open up new possibilities for a form of therapy. It could be enzyme replacement therapy.

Outlook & Forecast

The prognosis of the disease must be evaluated individually. Despite all efforts, some patients show only a small improvement in their state of health. In other cases, however, a longer period of freedom from symptoms could be achieved through medical care. However, recovery does not occur. The time of diagnosis and the start of treatment are primarily dependent on the course of the disease. The earlier the disease is detected, the better the prognosis.

The best results so far have been seen in a pre-symptomatic stage. In some cases, surgery can significantly improve the situation. Nevertheless, the transplantation of bone marrow or stem cells is associated with numerous risks. If the operation proceeds without further disturbances, the best results are usually achieved. In addition, symptomatic therapy is initiated. This is designed according to the individual complaints and is in most cases adapted to developments over time. In addition, the person concerned should use a special diet as part of self-help. This also leads to an alleviation of the existing health irregularities.

Without seeking medical help, an increase in symptoms is to be expected. It can lead to cognitive losses, seizures or subsequent psychological disorders. In these patients, the prognosis is significantly worse.


Since it is a hereditary disease, preventive measures are not available. The only alternative remains to recognize the symptoms in good time and start treatment as early as possible.

You can do that yourself

Patients with metachromatic leukodystrophy usually suffer from a significantly reduced quality of life and are dependent on the support of other people in everyday life, especially in advanced stages of the disease. Even as children, those affected suffer from motor disorders, which become noticeable when walking or coordinating movements.

In order to prevent social exclusion among children, it is advisable to attend a special school. There are often helpful social contacts that improve the patient’s attitude towards life. Since in some cases those affected suffer from learning difficulties that increase with age, they also receive appropriate pedagogical care in special institutions.

The physical symptoms of metachromatic leukodystrophy are partially reduced by taking the prescribed medication in a disciplined manner, which is usually a purely symptomatic therapy. In order to improve the motor skills of the patients, regular appointments with a physiotherapist are appropriate. There, those affected also learn physiotherapy exercises, which can also be carried out on their own.

As the disease progresses, the independence of the patients decreases, so that they need the help of relatives or nursing staff to cope with their everyday life. Sometimes psychotherapeutic support is needed.


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