Metachromatic Leukodystrophy

Metachromatic leukodystrophy (MLD) is one of a group of genetic disorders called the leukodystrophies. These diseases impair the growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers. Myelin, which lends its color to the white matter of the brain, is a complex substance made up of a mixture of fats and proteins.  Some leukodystrophies are caused by genetic defects of enzymes that regulate the metabolism of fats needed in myelin synthesis.  MLD is cause by a deficiency of the enzyme arylsulfatase A.  MLD is one of several lipid storage diseases, which result in the toxic buildup of abnormal fatty materials (lipids), which interfere with the normal fats and proteins in the myelin sheath.  There are three forms of MLD: late infantile, juvenile, and adult. Onset of the late infantile form (the most common MLD)  is typically between 12 and 20 months following birth.  Affected children have difficulty walking after the first year of life. 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. Most children with this form of MLD die by age 5. The juvenile form of MLD (between 3-10 years of age) usually begins with impaired school performance, mental deterioration, and dementia and then develop symptoms similar to the infantile form but with slower progression. The adult form commonly begins after age 16 as a psychiatric disorder or progressive dementia. Symptoms include impaired concentration, ataxia, seizures, dementia, and tremor..

There is no cure for MLD.  Bone marrow transplantation may delay progression of the disease in some infantile-onsetcases. Other treatment is symptomatic and supportive. Considerable progress has been made with regard to gene therapy in an animal model of MLD.

The prognosis for MLD is poor. Most children within the infantile form die by age 5. Symptoms of the juvenile form progress with death occurring 10 to 20 years following onset.  Those persons affected by the adult form typically die withing 6 to 14 years following onset of symptoms.

The National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health (NIH), conducts research on the lipid storage diseases in laboratories at the NIH and also supports additional research through grants to major medical institutions across the country.A combination of gene therapy and transplantation of the patient's own bone marrow cells is currently ongoing in Europe and being discussed the the U.S. Food and Drug Administration in the United States.  A trial of Arylysulfatase A has been completed in late infantile MLD in the United States and results are not yet published.

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