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Leukodystrophy, Metachromatic

Synonyms of Leukodystrophy, Metachromatic

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

Disorder Subdivisions

  • Adult Metachromatic Leukodystrophy
  • Juvenile Metachromatic Leukodystrophy
  • Late Infantile Metachromatic Leukodystrophy

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.

Related Disorders

Symptoms of the following disorders can be similar to those of metachromatic leukodystrophy. Comparisons may be useful for a differential diagnosis:

Adrenoleukodystrophy is a rare inherited metabolic disorder characterized by the loss of the fatty covering (myelin sheath) on nerve fibers within the brain (cerebral demyelination) and the progressive degeneration of the adrenal gland (adrenal atrophy). Increased levels of very long chain fatty acids (VLCFA) accumulate in the blood plasma and other tissues of the body. The most common form of the disease occurs during childhood. Symptoms may include: behavioral changes such as poor memory, increasingly poor school work, loss of emotional control, and/or dementia. Other symptoms may include the impaired ability to coordinate movement (ataxia), exaggerated reflex responses (hyperreflexia), muscle weakness on one side of the body (hemiparesis), speech difficulties, hearing loss, and/or visual difficulties. (For more information on this disorder, choose "Adrenoleukodystrophy" as your search term in the Rare Disease Database.)

Alexander's disease is an extremely rare progressive metabolic disorder that is frequently inherited. It is one of a group of diseases known as the Leukodystrophies. Alexander's disease is characterized by the loss of the fatty layers that cover the nerve fibers. The symptoms of the disorder usually begin during infancy and may include muscle spasms, developmental delays, seizures, and/or mental retardation. When Alexander's disease begins during childhood, the symptoms may include difficulty swallowing, painful joints, vomiting, difficulty breathing, the inability to cough, and/or muscle spasms. (For more information on this disorder, choose "Alexander" as your search term in the Rare Disease Database.)

Canavan disease is a rare inherited neurological disorder characterized by spongy degeneration of the brain and spinal cord (central nervous system). Symptoms may include lack of muscle tone (hypotonia), the loss of previously acquired mental, motor, and/or physical skills, poor head control, an abnormally enlarged head (megalocepahly), and/or blindness. Other symptoms may include involuntary muscle contractions of the arms and legs, exaggerated reflex responses, weakness of the muscles that support the head (atonicity), and/or paralysis. Canavan disease is caused by a deficiency of the enzyme aspartoacylase. Symptoms may begin during early infancy and usually progress rapidly, resulting in life-threatening complications. (For more information on this disorder, choose "Canavan" your search term in the Rare Disease Database.)

Krabbe's leukodystrophy is a rare inherited metabolic disorder characterized by the abnormal accumulation of a fatty substance (ceremide galactoside) in the brain. Symptoms develop due to a deficiency of the enzyme galactoside beta-galactosidase and may include irritability, vomiting, episodes of partial unconsciousness, and/or seizures. There may also be spastic contractions of the legs, difficulty swallowing, and/or mental deterioration. (For more information on this disorder, choose "Krabbe" as your search term in the Rare Disease Database.)

Tay-Sach disease is a rare inherited disorder that results in the progressive destruction of the central nervous system. The body is unable to properly metabolize certain fats (lipids) due to the absence of an enzyme (hexosaminidase A). This results in the accumulation of these fats in the brain (GM2 gangliosidosis). Symptoms may include an abnormal startle response and muscle spasms (myoclonic jerks). Between 6 and 10 months of age, additional symptoms appear including feeding difficulties, muscle weakness (hypotonia), restlessness, unusual eye movements, and red circular spots in the eyes (cherry red macular spots). After 12 months affected children may lose previously acquired skills and coordination. Tay-Sach disease is generally found among children of Eastern European Jewish heritage. (For more information on this disorder, choose "Tay-Sachs" as your search term in the Rare Disease Database.)

Sandhoff disease is a rare inherited lipid storage disease resulting in the progressive deterioration of the central nervous system. A deficiency of the enzyme hexosaminidase (beta-subunit) results in the accumulation of certain fats in the brain and other organs of the body. Sandhoff disease is a severe form of Tay-Sachs disease and is not limited to any particular ethnic group. The first symptoms of Sandhoff disease typically begin between the ages of 3 to 6 months and may include feeding problems, general weakness, an exaggerated startle reflex, motor weakness, and/or red spots (cherry macules) in the eyes. Other symptoms may include progressive mental deterioration, spasticity, heart murmurs, seizures (myoclonic and generalized), blindness, and/or an abnormally enlarged spleen. (For more information on this disorder, choose "Sandhoff" as your search term in the Rare Disease Database.)

Pelizaeus-Merzbacher brain sclerosis is a rare inherited disease of the central nervous system that is associated with the progressive deterioration of the white matter of the brain. The symptoms may begin during infancy (classical form of the disease) or adulthood. In infants, symptoms may include failure to develop normal control of the head and eyes, growth delays, muscle tremors, weakness, involuntary jerky muscle movements, facial grimacing, unsteadiness, and/or the abnormal permanent fixation of joints (contractures). (For more information on this disorder, choose "Pelizaeus- Merzbacher" as your search term in the Rare Disease Database.)

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 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

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

Organizations related to Leukodystrophy, Metachromatic


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The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2008/05/14 00:00:00 GMT+0

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