Metachromatic leukodystrophy (MLD, also referred to as arylsulfatase A deficiency) is a lysosomal storage disorder that’s often recorded in the family of leukodystrophies in addition to one of the sphingolipidoses since it affects the metabolism of sphingolipids. Leukodystrophies have an effect on the development and/growth of myelin, the fatty covering that acts as an insulator around nerve fibers through the central and peripheral nervous systems. MLD entails cerebroside sulfate accumulation. Metachromatic leukodystrophy, such as most enzyme deficiencies, comes with an autosomal recessive inheritance pattern.
Signs and symptoms
Like many other genetic disorders that affect lipid metabolism, there are several forms of MLD, which are late infantile, juvenile, and adult.
- In the late infantile form, which is the most common form of MLD (50–60%), affected children begin having difficulty walking after the first year of life, usually at 15–24 months. Symptoms include muscle wasting and weakness, muscle rigidity, developmental delays, progressive loss of vision leading to blindness, convulsions, impaired swallowing, paralysis, and dementia. Children may become comatose. Untreated, most children with this form of MLD die by age 5, often much sooner.
- Children with the juvenile form of MLD (onset between 3 and 10 years of age) usually begin with impaired school performance, mental deterioration, and dementia and then develop symptoms similar to the late infantile form but with slower progression. Age of death is variable, but normally within 10 to 15 years of symptom onset although some juveniles can live for several decades or longer after onset.
- The adult form commonly begins after age 16 often with an onset in the 4th or 5th decade of life and presents as a psychiatric disorder or progressive dementia. Adult-onset MLD usually progresses more slowly than the late infantile and juvenile forms, with a protracted course of a decade or more.
Palliative care can help with many of the symptoms and usually improves quality of life and longevity.
Carriers have low enzyme levels compared to their family population (“normal” levels vary from family to family) but even low enzyme levels are adequate to process the body’s sulfatide.
Causes of Metachromatic Leukodystrophy
MLD is directly caused by a lack of this enzyme arylsulfatase A (ARSA) and is distinguished by enzyme action in leukocytes that’s less than 10 percent of regular controls. But, assay of this ARSA enzyme action alone isn’t adequate for identification; ARSA pseudodeficiency, that is distinguished by enzyme action that’s 5~20 percent of ordinary controls does not trigger MLD. With this enzyme, sulfatides develop in several tissues of the body, finally destroying the myelin sheath of the nervous system. The myelin sheath is a fatty covering that protects nerve fibers. Without it, the nerves in the brain (central nervous system — CNS) and the peripheral nerves (peripheral nervous system — PNS) that restrain, one of the things that the muscles associated with mobility, stop to operating properly.
Treatment of Metachromatic Leukodystrophy
There’s now no treatment or cure for MLD in late infantile patients displaying symptoms, or for juvenile and adult beginning with complex symptoms. These individuals typically receive clinical therapy centered on symptom and pain management.
Pre-symptomatic late infantile MLD patients, in addition to people with adult or juvenile MLD who are either presymptomatic or displaying symptoms that are mild, may contemplate bone marrow transplantation (such as stem cell transplantation), which might slow down development of the disorder in the central nervous system. However, results from the peripheral nervous system are less striking, and also the long-term outcomes of these remedies are mixed. Recent success has entailed stem cells being obtained in the bone marrow of children with the disease and infecting the cells using a retro-virus, replacing the stem cells’ mutated gene together with the fixed receptor prior to re-injecting it back into the patient where they multiplied. The kids by age five were all in good shape and visiting kindergarten when generally by this age, kids with the disease can’t even speak.