Metachromatic leukodystrophyMLD; Arylsulfatase A deficiency; Leukodystrophy - metachromatic; ARSA deficiency
Metachromatic leukodystrophy (MLD) is a genetic disorder that affects nerves, muscles, other organs, and behavior. It slowly gets worse over time.
MLD is usually caused by the lack of an important enzyme called arylsulfatase A (ARSA). Because this enzyme is missing, chemicals called sulfatides build up in the body and damage the nervous system, kidneys, gallbladder, and other organs. In particular, the chemicals damage the protective sheaths that surround nerve cells.
Enzymes are complex proteins that cause a specific chemical change in all parts of the body. For example, they can help break down the foods we eat ...
The disease is passed down through families (inherited). You must get a copy of the defective gene from both your parents to have the disease. Parents can each have the defective gene, but not have MLD. A person with one defective gene is called a "carrier."
Children who inherit only one defective gene from one parent will be a carrier, but usually will not develop MLD. When two carriers have a child, there is a 1 in 4 chance that the child will get both genes and have MLD.
MLD occurs in about 1 in 40,000 people. There are three forms of the disease. The forms are based on when the symptoms begin:
- Late infantile MLD symptoms usually begin by ages 1 to 2.
- Juvenile MLD symptoms usually begin between ages 4 and 12.
- Adult (and late-stage juvenile MLD) symptoms may occur between age 14 and adulthood (over age 16), but may begin as late as the 40s or 50s.
Symptoms of MLD may include any of the following:
- Abnormally high or decreased muscle tone, or abnormal muscle movements, any of which may cause problems walking or frequent falls
Behavior problems, personality changes,
Young children who cannot talk yet will let you know when something is wrong by acting fussy or irritable. If your child is fussier than usual, it c...
- Decreased mental function
- Difficulty swallowing
- Inability to perform normal tasks
Urinary (or bladder) incontinence happens when you are not able to keep urine from leaking out of your urethra. The urethra is the tube that carries...
- Poor school performance
A seizure is the physical findings or changes in behavior that occur after an episode of abnormal electrical activity in the brain. The term "seizure...
- Speech difficulties, slurring
Exams and Tests
The health care provider will perform a physical exam, focusing on the nervous system symptoms.
Tests that may be done include:
- Blood or skin culture to look for low arylsulfatase A activity
- Blood test to look for low arylsulfatase A enzyme levels
- DNA testing for the ARSA gene
of the brain
A magnetic resonance imaging (MRI) scan is an imaging test that uses powerful magnets and radio waves to create pictures of the body. It does not us...
A nerve biopsy is the removal of a small piece of a nerve for examination.
- Nerve signaling studies
Urinalysis is the physical, chemical, and microscopic examination of urine. It involves a number of tests to detect and measure various compounds th...
There is no cure for MLD. Care focuses on treating the symptoms and preserving the person's quality of life with physical and occupational therapy.
Bone marrow transplant may be considered for infantile MLD.
Research is studying ways to replace the missing enzyme (arylsulfatase A).
For additional information and resources, see:
- United Leukodystrophy Association -- www.ulf.org
- MLD Foundation -- www.mldfoundation.org
MLD is a severe disease that gets worse over time. Eventually, people lose all muscle and mental function. Life span varies, depending on what age the condition started, but the disease course usually runs 3 to 20 years or more.
People with this disorder are expected to have a shorter than normal lifespan. The earlier the age at diagnosis, the more quickly the disease progresses.
Genetic counseling is recommended if you have a family history of this disorder.
Kwon JM. Neurodegenerative disorders of childhood. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. Philadelphia, PA: Elsevier; 2016:chap 599.
Pastores GM. Lysosomal storage diseases. In: Swaiman KF, Ashwal S, Ferriero DM, Schor NF, eds. Swaiman's Pediatric Neurology . 5th ed. Philadelphia, PA: Elsevier; 2012:chap 36.
Central nervous system and peripheral nervous system - illustration
The central nervous system is comprised of the brain and spinal cord. The peripheral nervous system includes all peripheral nerves.
Central nervous system and peripheral nervous system
Review Date: 10/30/2016
Reviewed By: Anna C. Edens Hurst, MD, MS, Assistant Professor in Medical Genetics, The University of Alabama at Birmingham, Birmingham, AL. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team.