Metachromatic Leukodystrophy

Overview

What is Metachromatic Leukodystrophy?

Metachromatic leukodystrophy (MLD) is one of a group of genetic disorders called the leukodystrophies. These diseases impair 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. Some leukodystrophies are caused by genetic defects of enzymes that regulate the metabolism of fats needed in myelin synthesis. MLD is cause by a deficiency of the enzyme arylsulfatase A. MLD is one of several lipid storage diseases, which result in the toxic buildup of abnormal fatty materials (lipids), which interfere with the normal fats and proteins in the myelin sheath. There are three forms of MLD: late infantile, juvenile, and adult. Onset of the late infantile form (the most common MLD) is typically between 12 and 20 months following birth. Affected children have difficulty walking after the first year of life. Symptoms include muscle wasting and weakness, muscle rigidity, developmental delays, progressive loss of vision leading to blindness, convulsions, impaired swallowing, paralysis, and dementia. Children may become comatose. 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. The adult form commonly begins after age 16 as a psychiatric disorder or progressive dementia. Symptoms include impaired concentration, ataxia, seizures, dementia, and tremor..

Is there any treatment?

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.

What is the prognosis?

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 within 6 to 14 years following onset of symptoms.

What research is being done?

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 in laboratories at the NIH and also supports additional research through grants to major medical institutions across the country.

A combination of gene therapy and transplantation of the patient's own bone marrow cells is currently ongoing in Europe and being discussed the the U.S. Food and Drug Administration in the United States. A trial of Arylsulfatase A has been completed in late infantile MLD in the United States and results are not yet published.

Resources

Organizations

The Arc of the United States

1825 K Street, NW, Suite 1200

Washington, DC 20006

Phone: 301.565.3842

Toll-free: 800.433.5255

Fax: 301.565.3843 or 5342

Email: [email protected]

Myelin Project

P.O. Box 39

Pacific Palisades, CA 90272

Phone: 310.459.1071

Toll-free: 800.869.3546

Fax: 310.230.4298

Email: [email protected]

National Organization for Rare Disorders (NORD)

55 Kenosia Avenue

Danbury, CT 06810

Phone: 203.744.0100

Voicemail: 800.999.NORD (6673)

Fax: 203.798.2291

Email: [email protected]

National Tay-Sachs and Allied Diseases Association

2001 Beacon Street, Suite 204

Boston, MA 02135

Toll-free: 800.90.NTSAD (906.8723)

Fax: 617.277.0134

Email: [email protected]

United Leukodystrophy Foundation

2304 Highland Drive

Sycamore, IL 60178

Phone: 815.895.3211

Toll-free: 800.728.5483

Fax: 815.895.2432

Email: [email protected]

MLD Foundation

21345 Miles Drive

West Linn, OR 97068

Toll-free: 800.617.8387

Phone: 503.656.4808

Email: [email protected]

*Source: National Institutes of Health; National Institute of Neurological Disorders and Stroke*

Reviewed by a Cleveland Clinic medical professional.

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