Metachromatic Leukodystrophy

Gene : ARSA

What is Metachromatic leukodystrophy?

Metachromatic leukodystrophy (MLD) is an inherited disorder that affects the brain, spinal cord, and the peripheral nerves. This disorder is caused by a deficiency of the enzyme called arylsulfatase A, leading to a build up of fatty substances primarily in the cells of the nervous system, and progressive destruction of the white matter covering nerve fibers in the brain. The symptoms of MLD occur gradually in the individuals who previously appear healthy. Affected individuals have symptoms including progressive deterioration of intellectual functions and motor skills, loss of sensation in the extremities, seizures, paralysis, inability to speak, blindness, hearing loss, and eventually unresponsiveness. The age of onset varies from late infantile to adult. In the most common and severe form, symptoms begin between the ages of six months and two years and most affected children die by age 5. MLD progresses more slowly in the late onset forms and death varies from within 10 years to several decades after onset. There is no specific treatment available but medical surveillance and care may help to improve some symptoms and overall condition of life. One of the causes of MLD is pathogenic variants in the ARSA gene.

How is MLD inherited?

MLD is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

What does it mean to be a carrier?

There are generally no signs or symptoms associated with being a carrier for MLD. However, the risk to have a child affected with MLD is increased. Testing of reproductive partners is recommended for carriers of MLD.

How common is MLD?

MLD occurs throughout the world, affecting 1 in 40,000 to 1 in 160,000 newborns in different populations. The disease is much more frequent in isolated populations, affecting 1 in 75 newborns among Habbanite Jews, 1 in 8,000 newborns in certain Arab groups in Israel, and 1 in 2,500 newborns in populations from the western portion of the Navajo Nation.

Family References and Resources
Clinician References
What is Analyzed?
  • Full gene sequencing
Affected Systems





Carrier Rates
Detection Rate
Carrier Frequency
General Population > 90% 1 in 100

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