Arylsulfatase A deficiency

Definition

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

Alternative Names

Causes

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.

The disease is inherited as an autosomal recessive genetic disorder. This means you must get a copy of the defective gene from both your parents. Those who only get a defective gene from only one parent, the child usually does not develop MLD.

Parents can each have the defective gene, but not have MLD. A person with one defective gene is called a "carrier." When two carriers have a child, there is a 25% chance that the child will get both genes and have MLD.

MLD occurs in about 1 per 40,000 people. There are three forms of the disease. They are based on when the symptoms begin.

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

Symptoms

• Irritability
• Decreased muscle tone
• Abnormal high muscle tone, spasticity, abnormal muscle movements
• Frequent falls
• Decreased intellectual functioning
• Speech difficulties, slurring
• Feeding difficulties
• Swallowing difficulty
• Nerve function problems
• Seizures

Exams and Tests

Signs include:

• Decreased or absent deep tendon reflexes
• Abnormal eye movements
• Poor visual fixation
• Optic nerve atrophy
• Posture abnormalities
• Coma

Possible tests include:

• Nerve velocity conduction studies
• MRI
• CT scan
• Lumbar puncture
• Nerve biopsy
• Urine chemistry
• Urinalysis
• Blood or skin culture to look for low arylsulfatase A activity
• Blood test to look for low arylsulfatase A enzyme levels

Treatment

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 lacking enzyme (arylsulfatase A).

Support Groups

For additional information and resources, see the United Leukodystrophy Association at www.ulf.org.

Outlook (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.