Leukodystrophy, Metachromatic

National Organization for Rare Disorders, Inc.

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It is possible that the main title of the report Leukodystrophy, Metachromatic is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


  • Late-Onset Metachromatic Leukodystrophy
  • ARSA
  • Arylsulfatase A Deficiency
  • Cerebroside Sulfatase Deficiency
  • Diffuse Cerebral Sclerosis
  • Greenfield Disease
  • Metachromatic Form of Diffuse Cerebral
  • Metachromatic Leukoencephalopathy
  • MLD
  • Sulfatide Lipidosis
  • Sulfatidosis

Disorder Subdivisions

  • None

General Discussion

Metachromatic leukodystrophy, the most common form of leukodystrophy, is a rare inherited neurometabolic disorder affecting the white matter of the brain (leukoencephalopathy). It is characterized by the accumulation of a fatty substance known as sulfatide (a sphingolipid) in the brain and other areas of the body (i.e., liver, gall bladder, kidneys, and/or spleen). The fatty protective covering on the nerve fibers (myelin) is lost from areas of the central nervous system (CNS) due to the buildup of sulfatide. Symptoms of metachromatic leukodystrophy may include convulsions, seizures, personality changes, spasticity, progressive dementia, motor disturbances progressing to paralysis, and/or visual impairment leading to blindness.

Metachromatic leukodystrophy is inherited as an autosomal recessive trait. There are three forms of the disease that have similar symptoms. However, they are distinguished by the age of onset: infantile, juvenile, and adult forms of metachromatic leukodystrophy.


The early signs and symptoms of metachromatic leukodystrophy may be vague and gradual in onset, making this disorder difficult to diagnose. Subtle changes in thought processing (mentation), memory, and/or posture may be the first symptoms observed in people with this disorder. Occasionally the earliest symptom is a disturbance in vision or numbness somewhere in the body.

Late infantile metachromatic leukodystrophy is usually detected in the second year of life, most commonly before the age of 30 months. The initial signs of the late infantile form include irritability, diminished muscle tone, and gait disturbance.

Juvenile metachromatic leukodystrophy typically begins between the ages of 4 and 10 years. Adult or late-onset metachromatic leukodystrophy begins after 16 years of age most often during the third or fourth decade. The symptoms of all forms of the disease are similar. However, visual difficulties may be more pronounced in infants, while psychosis and dementia may be more severe in adults with this disease. Symptoms may vary greatly among affected individuals.

The symptoms of all forms of metachromatic leukodystrophy may include vision problems leading to blindness, personality changes, and motor disturbances such as clumsiness, muscle weakness (hypotonia), rigidity, inability to coordinate movement (ataxia), and/or muscle spasms especially of the neck, spine, arms, and legs. Other symptoms may include abdominal distention, difficulty speaking (dysarthria), loss of previously acquired intellectual skills, general mental deterioration, and/or seizures. As the symptoms of Metachromatic Leukodystrophy progress, blindness, paralysis, psychosis, and/or dementia may develop. Behavioral abnormalities and dementia are particularly pronounced in the adult-onset form of the disease.

Peripheral neuropathy may also occur in individuals with metochromatic leukodystrophy. Peripheral neuropathy is a general term that denotes a disorder of the peripheral nervous system. The peripheral nervous system consists of all the motor and sensory nerves that connect the brain and spinal cord to the rest of the body (i.e., the nerves outside the central nervous system). The symptoms and physical findings associated with peripheral neuropathies may be extremely complex and vary greatly from case to case. Common findings associated with peripheral neuropathy may include muscle weakness; pain; numbness; redness; and/or burning or tingling sensations in the affected areas, especially the arms and legs (extremities).


Metachromatic leukodystrophy is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.

The symptoms of metachromatic leukodystrophy develop due to a deficiency of the enzyme arylsulfatase A (cerebroside sulfatase), which acts on a certain substance (sulfatide) in the fatty covering on nerve fibers (myelin sheath) of the central nervous system's white matter. The gene that regulates the activity of arylsulfatase A has been located on the long arm of chromosome 22 (22q13.31qter). Low levels of this enzyme lead to the degeneration of the myelin and progressive neurological symptoms. The adult- onset form of this disease occurs because of defects in the protein that activates arylsulfatase activity, even though the quantity of the enzyme may be normal in some affected adults with metachromatic leukodystrophy.

Affected Populations

Metachromatic leukodystrophy is a rare disorder that affects males and females in equal numbers. People of all ethnic backgrounds may be affected by this disease. More than 160 cases have been reported in the medical literature. The prevalence of the late infantile form is 1 in 40,000. The prevalence of the juvenile form is 1 in 150,000.

The symptoms of the infantile form of metachromatic leukodystrophy typically begin by the age of two years. Juvenile metachromatic leukodystrophy usually begins between ages 4 and 10 years, and adult or late-onset metachromatic leukodystrophy typically begins after 16 years of age.

Standard Therapies

The diagnosis of Metachromatic Leukodystrophy is confirmed by a thorough medical evaluation and laboratory tests. A specialized urine test uses a dye (toluidine blue) to stain certain substances in the urine. The urinary sediment contains material (metachromatic galactosphingosulfatides) that appears red after staining. The levels of protein in the fluid that surrounds the brain and spinal cord (cerebrospinal fluid) are usually elevated.

The treatment for Metachromatic Leukodystrophy is symptomatic and supportive. The diagnosis of this disorder in a developing fetus (prenatal testing) is possible by measuring arylsulfatase A activity in cultured cells from the fluid that surrounds the fetus (amniotic fluid). These cells may be obtained during a special procedure during which amniotic fluid is extracted by syringe (amniocentesis) and then analyzed. Genetic counseling will be of benefit for families of children with Metachromatic Leukodystrophy.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:




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For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.