GM1 gangliosidosis

GM1 gangliosidosis is a hereditary condition that is inherited in an autosomal recessive manner.^[1][2] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has:

• a 25% (1 in 4) chance to be affected
• a 50% (1 in 2) chance to be an unaffected carrier like each parent
• a 25% chance to be unaffected and not be a carrier

GM1 gangliosidosis is type-specific within families. This means that people with a family history of the condition are generally only at increased risk for the specific type of GM1 gangliosidosis in the family.^[2]

Having a family history of GM1 gangliosidosis may mean that certain relatives are at risk to either be affected, be a carrier, or have children that are affected.

For an autosomal recessive condition like GM1 gangliosidosis:

• At conception, each sibling of an affected person has a 25% chance to be affected, a 50% chance to be an asymptomatic carrier, and a 25% chance to be unaffected and not a carrier.
• Once an at-risk sibling is known to be unaffected, the risk for him/her to be a carrier is 2/3 (about 67%).
• A carrier is generally not at risk to have an affected child unless his/her partner is also a carrier.
• Each child of a carrier has a 50% chance to be a carrier.
• While severely affected people with GM1 do not have children, the children of a mildly affected person will always be carriers.^[3]
• A person who has not inherited a disease-causing mutation from a parent (i.e. is not a carrier) is not at risk to pass it to his/her children, because the mutation has been eliminated from that lineage.

People with questions about genetic risks for themselves or family members are encouraged to speak with a genetics professional.

A diagnosis of GM1 gangliosidosis (GM1), can be made by either enzyme analysis of the beta-galactosidase enzyme, or by molecular genetic testing of the GLB1 gene. Despite the availability of molecular genetic testing, the mainstay of diagnosis will likely continue to be enzyme activity because of cost and difficulty in interpreting unclear results.^[3] However, enzyme activity may not be predictive of carrier status in relatives of affected people. Carrier testing for at-risk family members is done with molecular genetic testing, and is possible if the disease-causing mutations in the family are already known.^[3]

The Genetic Testing Registry (GTR) provides information about the labs that offer genetic testing for this condition. The intended audience for the GTR is health care providers and researchers. Therefore, patients and consumers with specific questions about a genetic test should contact a health care provider or 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.