Metachromatic Leukodystrophy (MLD)
Metachromatic Leukodystrophy is unusual among the leukodystrophies because, rather than being caused by too little of a myelin sheath component, it is caused by too much of one. A lack of the enzyme arylsulfatase A leads to a build up of sulfatides, a component of the myelin sheath, in the patient's nervous system in various organs in the body such as the kidney, liver, and gall bladder. The sulfatides are not properly broken down when the enzyme is missing.
Although Metachromatic Leukodystrophy, along with Adrenoleukodystrophy, is probably the most frequently observed leukodystrophy, the reason why this increase in sulfatide levels causes demyelination is as yet unknown
MLD is an autosomal recessive type of disorder, and manifests in three types:
- Late Infantile, with onset of symptoms between six months and two years of age;
- Juvenile, with onset of symptoms after age four until age sixteen years;
- Adult, with onset of symptoms after age sixteen and characterized by psychiatric disturbances evolving to dementia.
Only one form of MLD is seen within a family.
The infantile form strikes children after their first year. Until then the child will have been developing normally. Following onset, the disease follows a course of continuous, progressive nervous system involvement. This course is time variable, but is progressively downhill, with death usually occurring within three to six years.
The child will first become 'floppy' due to low muscle tone, and speech abnormalities may occur.
Soon after comes a halting of mental development, the loss of ability to make many voluntary movements. Mental abilities will be lost, and the child will be unable to speak or to see. Ultimately, the child will be bedridden. Swallowing ability is often lost, and the child will need to be tube fed.
MLD is usually diagnosed through blood and urine tests, together with clinical studies. In cases of MLD, the level of arylsulfatase A in the blood is very low, while sulfatide levels in the urine are increased. Carrier detection and prenatal diagnosis are available; genetic counselling is advised.
Bone marrow transplant has been used experimentally for children with the mild form of MLD.
Further information can be obtained from:
Metachromatic Leukodystrophy (MLD) [external]