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.
There is no cure for MLD. Bone marrow transplantation may delay progression of the disease in some infantile-onset cases. Other treatment is symptomatic and supportive. Considerable progress has been made with regard to gene therapy in an animal model of MLD and in clinical trials.
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 and also supports additional research through grants to major medical institutions across the country.
Studies of children with MLD are monitoring disease progression as it relates to overall motor skills. Another study is investigating the safety of the transplantation of human placental-derived stem cells (HPDSC) given in conjunction with umbilical cord blood (UCB) stem cells in individuals with various malignant or nonmalignant disorders such as MLD. Scientists also hope to determine whether immune tolerance and donor cell engraftment can be achieved through first trimester injection of donor cells to fetuses diagnosed with lysosomal storage diseases. Studies investigating other forms of treatment are being conducted outside the United States and are being discussed with the U.S. Food and Drug Administration.
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Last Modified September 3, 2015