Metachromatic leukodystrophy is a sphingolipidosis, an inherited disorder of metabolism, caused by arylsulfatase A deficiency. There are several forms, the most severe of which causes progressive paralysis and dementia resulting in death by age 10 years. Diagnosis is by DNA analysis and/or enzyme analysis of white blood cells or skin fibroblasts. Treatment is sometimes with bone marrow or stem cell transplantation.
For more information, see table Some Sphingolipidoses.
See also Approach to the Patient With a Suspected Inherited Disorder of Metabolism.
In metachromatic leukodystrophy, arylsulfatase A deficiency causes metachromatic lipids to accumulate in the white matter of the central nervous system, peripheral nerves, kidney, spleen, and other visceral organs; accumulation in the nervous system causes central and peripheral demyelination. Numerous mutations exist; patients vary in age at onset and speed of progression.
The infantile form is characterized by progressive paralysis and dementia usually beginning before age 4 years and resulting in death about 5 years after onset of symptoms.
The juvenile form manifests between 4 years and 16 years of age with gait disturbance, intellectual impairment, and findings of peripheral neuropathy. Contrary to the infantile form, deep tendon reflexes are usually brisk.
There is also a milder adult form.
Diagnosis of Metachromatic Leukodystrophy
Enzyme analysis
Diagnosis of metachromatic leukodystrophy is suggested clinically and by findings of decreased nerve conduction velocity; it is confirmed by DNA analysis and/or detecting enzyme deficiency in white blood cells or cultured skin fibroblasts. (See also testing for suspected inherited disorders of metabolism.)
Treatment of Metachromatic Leukodystrophy
Sometimes bone marrow or stem cell transplantation
There is currently no effective treatment for metachromatic leukodystrophy in patients with advanced symptoms.
Bone marrow or stem cell transplantation may stabilize neurocognitive function in mildly symptomatic forms of the disease.
Several other therapeutic options are currently being investigated, primarily in late infantile forms of the disease, including gene therapy, enzyme replacement therapy, substrate reduction therapy, and, potentially, enzyme enhancement therapy.
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Online Mendelian Inheritance in Man (OMIM) database: Complete gene, molecular, and chromosomal location information
