Metachromatic leukodystrophy is a genetic disease which alters the normal growth and development of the myelin, which is a fatty substance that insulates and protects nerve cells axons, affecting the nerves and muscles. Metachromatic leukodystrophy is caused by a deficiency of the enzyme arylsulfatase A. When this enzyme is missing, sulfatides build up in many tissues of the body, eventually destroying the myelin sheath of the nervous system, as well as kidneys, gallbladder, and other organs. This disease gets worse over time.
There are several forms of metachromatic leukodystrophy, 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.
Children with the juvenile form of MLD (onset between 3–10 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 as a psychiatric disorder or progressive dementia. Adult-onset MLD 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 and longevity of life. Carriers have low enzyme levels compared to their family population but even low enzyme levels are adequate to process the body's sulfatide.
There is no cure for MLD, and no standard treatment. It is a terminal illness. Children with advanced juvenile or adult onset, and late infantile patients displaying symptoms have treatment limited to pain and symptom management.