Metachromatic leukodystrophy

Definition

Metachromatic leukodystrophy (MLD) is a genetic disorder that affects nerves, muscles, and other organs. It gets progressively worse over time.

MLD is usually caused by the lack of an important enzyme called arylsulfatase A. Because this enzyme is missing, chemicals called sulfatides accumulate in the nervous system, kidneys, gallbladder, and other organs. The sulfatides damage the nerves and organs where buildup occurs. In particular, it damages the myelin sheaths that surround nerve cells.

There are three forms, based on when the symptoms begin:

• Late infantile -- symptoms usually begin by age 4. The symptoms include problems walking, loss of muscle control, and loss of mental functions.
• Juvenile -- symptoms begin between 4 and 6 years old. The child has trouble walking and loses developmental milestones. The first sign may be deteriorating school performance.
• Adult -- the late juvenile (age 6-16 age) and adult (over age 16) forms progress slowly. Early signs may be behavior problems, loss of mental functions, poor school or work performance, seizures, and loss of muscle control.

Causes, incidence, and risk factors

Metachromatic Leukodystrophy is caused by a mutation in the gene that makes arylsulfatase A. The disease is inherited as an autosomal recessive genetic disorder. This means that an affected person inherits a copy of the defective gene from both parents. A person who inherits a defective gene from only one parent is usually not affected.

When two "carrier" (unaffected) parents have a child, there is a 25% chance that the child will inherit the gene from both parents. If that happens, the child will have MLD.

Metachromatic Leukodystrophy occurs in about 1 per 40,000 people.

Symptoms

• irritability
• decreased muscle tone
• abnormal high muscle tone, spasticity, abnormal muscle movements
• falls frequently
• decreased intellectual functioning
• speech difficulties, slurring
• feeding difficulties
• swallowing difficulty
• nerve function abnormality
• seizures

Signs and tests

Signs include:

• decreased or absent deep tendon reflexes
• abnormal eye movements
• poor visual fixation
• optic nerve atrophy
• decorticate posturing
• coma

• nerve velocity conduction studies
• MRI
• CT scan
• lumbar puncture to examine the cerebrospinal fluid, which would show increased CSF total protein
• nerve biopsy -- the tissue is then stained to look for a particular color, or metachromatic, pattern
• urine chemistry -- to look for very high sulfatide levels
• urinalysis
• culture of skin fibroblasts or white blood cells -- to look for low arylsulfatase A activity
• blood test -- to look for low arylsulfatase A enzyme levels

Treatment

At present, there is no cure for MLD. Care focuses on treating the symptoms and preserving the patient's quality of life.

Research is ongoing to study techniques to replace the deficient enzyme, arylsulfatase A.

Support Groups

For additional information and resources, see the United Leukodystrophy Association at www.ulf.org or call 800-728-5483.

Expectations (prognosis)

MLD is a severely debilitating, progressive disease. The outlook is poor. Individuals with this disorder are expected to die prematurely. The earlier the age of diagnosis, the more rapid the progression.

Prevention

Genetic counseling is recommended if you have a family history of this disorder.

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