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Metachromatic Leukodystrophy (MLD)

Metachromatic leukodystrophy (MLD) which is also called as Arylsulfatase A deficiency comes under the group of lysosomal storage disease and belongs to leukodystrophies family. It is basically a rare genetic disorder that affects muscles, nerves and various other organs and this disorder slowly gets worse over time. A sphingolipid called sulfatide accumulates in various tissues of patients suffering from the disease. Sulfatide is derived from galactocerebroside through esterification of the hydroxyl group on carbon 3 of the galactose with sulfuric acid. The ratio of cerebroside to sulfatide in brain is normally about 3:1. This value is drastically altered in MLD. Therre appears to be some decrease in cerebroside, along with an accumulation of sulfatide, so that in patients with MLD the ratio of cerebroside to sulfatide is approximately 1:4.

There are two clinically distinguishable forms of MLD.

Late infantile variety

The first is called the late infantile variety, in which the disease becomes evident before the thirtieth month of life. This form is accompanied by obvious signs and symptoms of central nervous system disease which includes defects in locomotion, weakness, ataxia, hypotonus and paralyses. Difficulties in speech and swallowing occur as the disease progresses and, in time, optic atrpohy appears.

Adult form

In the second, or adult form, the initial symptoms are primarily manifested as psychological difficulties. The patients subsequently show evidence of progressive dementia.

In both forms of MLD, there is a diffuse loss of myelin in the central nervous system. The peripheral nerves are also invloved, and brown-staining droplets are seen along the nerves after tissue sections are treated with cresyl violet. Similar deposits are seen around the nerves of the appendix and myelinated nerve fibres of the dental pulp. There is a decrease in nerve conduction velocity in this disease, a finding which is not observed in other sphingolipidoses. There are also metachromatic deposits in the kidney and bile ducts, accompanied by an impairment of gall-bladder function. The biochemcial defect in MLD is a deficiency of the enzyme which catalyzes the hydroysis of sulfatide.

See the Chemical Reaction Below

The defective enzyme is generally designated as arylsulfatase because nits catalytic activity is frequently determined using aryl sulfate esters as substrate.

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