Metachromatic Leukodystrophy

Metachromatic leukodystrophy (MLD) is one of a group of genetic disorders called the leukodystrophies, which are characterized by the toxic buildup of lipids (fatty materials such as oils) and other storage materials in cells in the white matter of the central nervous system and peripheral nerves.  The buildup of storage materials impairs 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.)  MLD is one of several lipid storage diseases, which result in the harmful buildup of lipids in brain cells and other cells and tissues in the body.  People with lipid storage diseases either do not produce enough of one of the enzymes needed to break down (metabolize) lipids or they produce enzymes that do not work properly.  Some leukodystrophies are caused by genetic defects of enzymes that regulate the metabolism of fats needed in myelin synthesis.  MLD, which affects males and females, is cause by a deficiency of the enzyme arylsulfatase A.  MLD has three forms: late infantile, juvenile, and adult. Late infantile MLD (the most common form)  typically begins between 12 and 20 months following birth.  Infants appear normal at first but develop difficulty walking after the first year of life and eventually lose the ability to walk.  Other symptoms include muscle wasting and weakness, muscle rigidity, developmental delays, progressive loss of vision leading to blindness, convulsions, impaired swallowing, and dementia. 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.  Death eventually occurs between 10 and 20 years of disease onset..   The adult form commonly begins after age 16, with symptoms that include psychiatric disturbances, seizures, tremor, impaired concentration, and dementia.  Death generally occurs within 6 to 14 years after onset of symptoms.