Metachromatic leukodystrophy

Metachromatic leukodystrophy is inherited in an autosomal recessive manner. This means that both copies of the disease-causing gene in each cell must have a mutation for an individual to be affected. Individuals inherit two copies of each gene - one copy from each parent. Typically, an individual is affected because they inherited a mutated copy of the gene from each parent. Individuals with one mutated copy of the gene (such as an unaffected parent of an affected individual) are referred to as carriers; carriers typically do not have any signs or symptoms of the condition.

When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) chance to have the condition, a 50% (1 in 2) chance to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Each sibling of a carrier for metachromatic leukodystrophy (MLD) has a 50% chance to also be a carrier. A carrier for MLD has one mutated copy of the disease-causing gene in each cell (as well as one normal copy). Typically, a carrier will have inherited the mutated copy from a carrier parent. A carrier parent, who also has one mutated copy and one normal copy of the gene, will randomly pass one of these copies on to each child. Therefore, at conception, each child of a carrier has a 50% (1 in 2) chance inherit the mutated copy and be a carrier, and a 50% chance to inherit the normal copy and not be a carrier.

If someone has a family history of metachromatic leukodystrophy (MLD) or someone is known to be a carrier for MLD, individuals who are biologically related to the affected individual or carrier are at risk to be a carrier. Generally speaking, the more closely related an individual is to the affected individual or carrier, the greater the chance for that person to be a carrier. Prior to genetic testing, the chance to be a carrier for some biological relatives of an affected individual are as follows:

• Parent of affected individual: assumed to be 100% (called an obligate carrier)
• Unaffected sibling of affected individual: 2 in 3 (~66.6%)
• Aunt or uncle of affected individual: 1 in 2 (50%)
• First cousin of affected individual: 1 in 4 (25%)

If someone has carrier testing and is found to be negative (not a carrier), that person's children are typically assumed to be negative also.

More information about the use of genetic carrier testing is available on GeneTests' Web site and can be viewed by clicking here.

Individuals who are interested in learning about genetic testing and about their specific risk to be a carrier should speak with a genetics professional.

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.