Detailed Information on Metachromatic Leukodystrophy

Metachromatic leukodystrophy (MLD) is a inherited disorder that affects nerves, muscles, and other organs. It slowly gets worse over time. Metachromatic leukodystrophy is reported to occur in 1 in 40,000 to 160,000 individuals worldwide. MLD is caused by a lack of the arylsulfatase an enzyme. Without this enzyme, lipids accumulate in the cells of the nervous system, liver, and kidneys. This accumulation of lipids eventually destroys the myelin sheath.  There are three forms of Metachromatic Leukodystrophy. They are based on when the symptoms begin.

Late infantile MLD symptoms usually begin by age 4 and include walking problems and loss of muscle control and mental functions. Children with the juvenile form of MLD (beginning between 3-10 years of age) frequently start with injured school performance, mental deterioration, and dementia and then grow symptoms similar to the late infantile form but with slower progression.  Adult and late-stage juvenile MLD symptoms usually occur slowly. They may occur between age 6-16 and adult. Early symptoms include behavior problems, loss of mental functions and muscle control, poor school or work performance, and seizures.

Commonly, children affected with MLD are misdiagnosed firstly. Misdiagnoses among affected adults include a variety of psychological conditions since the disease first manifests with psychological symptoms. Symptoms of Metachromatic Leukodystrophy involve muscle wasting and weakness, muscle rigidity, developmental delays, advanced loss of vision leading to blindness, convulsions, impaired swallowing, paralysis, and dementia. There is no cure for MLD. Bone marrow transplantation (including stem cell transplantation), which may slow down the progression of the disease, or stop its progression in the central nervous system.

However results in the peripheral nervous system have been less dramatic and the long-term effects of these therapies have show mixed results. Other treatment is symptomatic and supportive. Treatment options for the future that are currently being analyzed include gene therapy and enzyme replacement therapy (ERT), substrate reduction therapy (SRT), and potentially an enzyme enhancement therapy (EET). A therapeutic strategy useful in other metabolic storage diseases is direct enzyme replacement. The difficulty with this strategy has always been getting adequate enzyme activity into the CNS.