Metachromatic Leukodystrophy: Symptoms, Causes, Affected Populations, Related Disorders, Diagnosis and Treatment

It is a rare hereditary neurometabolic disorder that affects the brain’s white matter (leukoencephalopathy).

It accumulates a fatty substance known as sulfatide (a sphingolipid) in the brain and other body areas (i.e., liver, gallbladder, kidneys, and spleen).

The protective fatty coating of the nerve fibers (myelin) is lost in the central nervous system (CNS) areas due to the accumulation of sulfatide.

Symptoms of metachromatic leukodystrophy may include seizures, personality changes, spasticity, progressive dementia, motor disorders that progress to paralysis, and visual impairment that lead 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: infant, juvenile, and adult.

Signs and symptoms

The first signs and symptoms of metachromatic leukodystrophy may be vague and of gradual onset, which makes this disorder difficult to diagnose. Subtle changes in thought processing (mentation), memory, and posture may be the first symptoms observed in people with this disorder.

Occasionally, the earliest symptom is an alteration in vision or numbness somewhere in the body.


Late metachromatic infantile leukodystrophy is usually detected in the second year of life, most commonly before 30 months. Early signs of the delayed immature form include irritability, decreased muscle tone, and impaired gait.

Juvenile metachromatic leukodystrophy usually begins between the ages of 4 and 10 years. Metachromatic leukodystrophy in adults or delayed onset starts after age 16, 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 babies, while psychosis and dementia may be more severe in adults with this disease. The symptoms can vary a lot between the people affected.

Symptoms of metachromatic leukodystrophy may include vision problems that lead to blindness, personality changes, and motor disorders such as clumsiness, muscle weakness ( hypotonia ), stiffness, inability to coordinate movement ( ataxia ), and muscle spasms, significantly of the neck, spine, arms, and legs.

Other symptoms may include abdominal distension, difficulty speaking ( dysarthria ), loss of previously acquired intellectual abilities, general mental deterioration, and seizures. As the symptoms of metachromatic leukodystrophy progress, they may develop blindness, paralysis, psychosis, and dementia.

Behavioral abnormalities and dementia are particularly pronounced in the form of the disease that begins in the adult.

Peripheral neuropathy can also occur in individuals with metachromatic leukodystrophy. Peripheral neuropathy is a general term that denotes a peripheral nervous system disorder.

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 (the nerves outside the central nervous system).

Symptoms and physical findings associated with peripheral neuropathies can be highly complex and vary significantly from case to case.

Common findings associated with peripheral neuropathy may include muscle weakness, pain; numbness; redness, and sensations of burning or tingling in the affected areas, especially the arms and legs (extremities).


Metachromatic leukodystrophy is inherited as an autosomal recessive trait. Two genes determine genetic diseases; one received from the father and the other 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 a normal gene and a gene for the disease, the person will be a carrier of the disease but usually will not have symptoms.

The risk of two carrier parents passing the defective gene and having an affected child is 25% each pregnancy.

The risk of having a child who is a carrier like the parents is 50% with each pregnancy. The probability that a child receives normal genes from both parents and is genetically normal for that trait is 25%.

The symptoms of metachromatic leukodystrophy develop due to a deficiency of the enzyme arylsulfatase A (brain sulphatase), which acts on a particular substance (sulfatide) in the fatty coating of the nerve fibers ( myelin sheath ) of the white matter of the brain. Central Nervous System.

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 myelin degeneration and progressive neurological symptoms.

The onset of this disease in adults occurs due to defects in the protein that activates arylsulfatase activity. However, the amount of the enzyme may be expected in some adults affected with metachromatic leukodystrophy.

Affected populations

Metachromatic leukodystrophy is a rare disorder that affects men and women in equal numbers. People of all ethnic backgrounds can be affected by this disease.

More than 160 cases have been reported in the medical literature. The prevalence of late childhood form is 1 in 40,000. The majority of the juvenile form is 1 in 150,000.

Symptoms of the infantile form of metachromatic leukodystrophy usually begin at two. Juvenile metachromatic leukodystrophy usually starts between 4 and 10 years, and metachromatic leukodystrophy of late-onset or in adults usually starts after 16 years of age.

Related disorders

The symptoms of the following disorders may be similar to those of metachromatic leukodystrophy. The comparisons can be helpful for a differential diagnosis:


Adrenoleukodystrophy is a rare hereditary metabolic disorder that is characterized by the loss of the fatty coating (myelin sheath) on the nerve fibers of the brain (cerebral demyelination) and the progressive degeneration of the adrenal gland ( adrenal atrophy ).

Increased levels of very-long-chain fatty acids (VLCFA) build up in blood plasma and other body tissues.

The most common form of the disease occurs during childhood. Symptoms may include behavioral changes such as poor memory, increasingly poor schoolwork, loss of emotional control, and dementia.

Other symptoms may include limited ability to coordinate movement (ataxia), exaggerated reflex responses ( hyperreflexia ), muscle weakness on one side of the body (hemiparesis), speech difficulties, hearing loss, and visual difficulties.

Alexander’s disease

Alexander’s disease is a sporadic progressive metabolic disorder that is often inherited. It is one of a group of diseases known as leukodystrophies.

Alexander’s disease is characterized by losing the nerve fibers’ fatty layers. Symptoms of the disorder usually begin during childhood and may include muscle spasms, developmental delays, seizures, and mental retardation.

When Alexander’s disease begins during childhood, symptoms may include difficulty swallowing, joint pain, vomiting, difficulty breathing, inability to cough, and muscle spasms.

Canavan disease

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 ), loss of previously acquired mental, motor, or physical skills, poor head control, an abnormally enlarged head (megalocephaly), and blindness.

Other symptoms may include involuntary muscle contractions of the arms and legs, exaggerated reflex responses, weakness of the muscles that support the head (atony), and paralysis.

A deficiency of the enzyme aspartoacylase causes Canavan disease. Symptoms can begin during early childhood and usually progress rapidly, resulting in life-threatening complications.

Leucodistrofia de Krabbe

Krabbe leukodystrophy is a rare hereditary metabolic disorder characterized by the abnormal accumulation of a fatty substance (galamide galactoside) in the brain.

Symptoms develop due to a deficiency of the enzyme galactosidase beta-galactosidase and may include irritability, vomiting, episodes of partial unconsciousness, and seizures. There may also be spastic contractions of the legs, difficulty swallowing, and mental deterioration.

Tay-Sach disease

The day-Sach disease is a rare inherited disorder that causes the progressive destruction of the central nervous system. The body can not 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 (gangliosidosis GM2).

Symptoms may include an abnormal startle response and muscle spasms (myoclonic jerks).

Additional symptoms appear between 6 and 10 months of age, including eating difficulties, muscle weakness (hypotonia), restlessness, unusual eye movements, and red circular spots on the eyes (cherry red macular holes).

After 12 months, affected children may lose previously acquired skills and coordination. The day-Sach disease is usually found among Eastern European Jewish heritage children.

Sandhoff’s disease

Sandhoff’s disease is a rare hereditary disease of lipid storage that results in 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’s disease is a severe form of Tay-Sachs disease and is not limited to any particular ethnic group.

The first symptoms of Sandhoff disease usually begin between 3 to 6 months. They may include feeding problems, general weakness, an exaggerated startle reflex, motor weakness, and red spots (cherry spots) on the eyes.

Other symptoms may include progressive mental deterioration, spasticity, heart murmurs, seizures (myoclonic and generalized), blindness, and abnormally enlarged spleen.

Esclerosis cerebral de Pelizaeus-Merzbacher

Pelizaeus-Merzbacher cerebral sclerosis is a rare hereditary disease of the central nervous system associated with the progressive deterioration of the brain’s white matter. Symptoms may begin during childhood (a classic form of the disease) or adulthood.

In infants, symptoms may include the inability to develop standard control of the head and eyes, growth retardation, muscle tremors, weakness, involuntary spasmodic muscle movements, facial grimaces, instability, and permanent fixation of the joints (contractures).


Your doctor will perform a physical examination, review your symptoms and medical history, and look for signs of metachromatic leukodystrophy.

Your doctor may order tests to diagnose your condition. These tests also help determine how difficult your situation is.

Blood and urine tests: Blood tests look for an enzyme deficiency that causes metachromatic leukodystrophy.

It is also possible that urine tests are done to verify the accumulation of fatty substances (lipids).

Genetic tests: Your doctor will perform genetic tests to detect mutations in the gene associated with metachromatic leukodystrophy.

You can also recommend screening for mutations in the gene to family members, especially pregnant women (prenatal tests).

Nerve conduction study: This test measures electrical nerve impulses and works on your muscles and nerves by passing a small current through electrodes in your skin.

Your doctor can use this test to look for nerve damage (peripheral neuropathy), typical in metachromatic leukodystrophy patients.

Magnetic Resonance Imaging (MRI): This test uses powerful magnets and radio waves to produce detailed images of your brain.

Your doctor can use this test to determine if you have metachromatic leukodystrophy, which has a characteristic (tigroid) striking pattern of abnormal white matter (leukodystrophy) in your brain.

Psychological and cognitive tests: Your doctor can evaluate your psychological and thinking (cognitive) skills. These tests can help determine how the condition affects your brain function.


Metachromatic leukodystrophy can not be cured, and there are few treatment options. However, your doctor should work with you to help you control your signs and symptoms and improve your quality of life.

Metachromatic leukodystrophy can be treated with several treatments:

Medications: Medications can reduce your signs and symptoms and relieve your pain.

Stem cell transplantation: Hematopoietic stem cell transplants have sometimes slowed the progression of metachromatic leukodystrophy by introducing healthy cells to help replace diseased cells.

Physical, occupational, and speech therapy: You may have physical therapy to promote muscle and joint flexibility and maintain your range of motion as much as possible. You may need a wheelchair, a walker, or other assistive devices as your condition progresses.

You may have occupational and speech therapy to improve your quality of life.

Nutrition Assistance: You and your family can work with a nutritionist (dietitian) to get the proper nutrition. Eventually, it may not be easy to swallow food or liquids.

You may need feeding devices as your condition progresses.

Synonyms of Metachromatic leukodystrophy

  • LAND.
  • Arylsulfatase A deficiency
  • Cerebroside sulfatase deficiency.
  • Diffuse cerebral sclerosis.
  • Enfermedad de Greenfield.
  • Late metachromatic leukodystrophy.
  • Metachromatic form of diffuse cerebral.
  • Leucoencefalopatía metacromática.
  • MLD.
  • Sulfatide Lipidosis.
  • Sulfatidosis.
  • Subdivisions of metachromatic leukodystrophy.
  • Adult Metachromatic Leukodystrophy.
  • Metachromatic Juvenile Leukodystrophy.
  • Metachromatic late childhood leukodystrophy.