Metachromatic leukodystrophyMLD; Arylsulfatase A deficiency; Leukodystrophy - metachromatic
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.
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 1 defective gene is called a "carrier."
Children who inherit only 1 defective gene from 1 parent will be a carrier, but usually will not develop MLD. When 2 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 3 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.
The symptoms for MLD are:
- Abnormally high muscle tone, abnormal muscle movements
- Behavior problems
- Decreased mental function
- Decreased muscle tone
- Difficulty walking
- Feeding difficulties
- Frequent falls
- Inability to perform normal tasks
- Loss of muscle control
- Nerve function problems
- Personality changes
- Poor school performance
- Speech difficulties, slurring
- Swallowing difficulty
Exams and Tests
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
- CT scan
- DNA testing for the ARSA gene
- Nerve biopsy
- Nerve signaling studies
- Urine chemistry
There is no cure for MLD. Care focuses on treating the symptoms and preserving the patient's quality of life with physical and occupational therapy.
Research is studying ways to replace the missing enzyme (arylsulfatase A).
For additional information and resources, see:
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 J, Schor N, Behrman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap 592.
Review Date: 11/25/2014
Reviewed By: Chad Haldeman-Englert, MD, FACMG, Wake Forest School of Medicine, Department of Pediatrics, Section on Medical Genetics, Winston-Salem, NC. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team.