Maple Syrup Urine Disease (MSUD) is a rare, autosomal recessive metabolic disorder in which the body is unable to process certain amino acids properly. It causes brain damage and progressive nervous system degeneration. MSUD is caused by mutations in three different genes: BCKDHA, BCKDHB and DBT (Warrell, Cox and Firth, 2012).
The BCKDHA gene causes MSUD Type Ia due to the mutation in the E1α subunit, BCKDHB causes Type Ib due to the mutation in the E1ᵦ subunit, and DBT causes Type II due to defect in the E2 subunit (Strauss, Puffenberger and Morton, 2006). Mutations in these genes result in decreased or absent activity of the human branched-chain α-keto acid dehydrogenase complex (BCKAD) enzymes, consisting of subunits E1α, β, E2 and E3. …show more content…
If an individual inherits one normal gene and one mutated gene, the person will be a carrier for MSUD. The risk for two carrier parents to both pass the mutated gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females according to the National Organization for Rare Disorders (NORD.
Parents who are close relatives have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with MSUD. For example, there is a much higher prevalence in the Amish community in Pennsylvania due to the founder affect.
There are four subtypes of MSUD. They differ by their degree of severity, enzyme activity, and the age when the disease arises.
Classic MSUD is the most common and severe form of the condition. A person with this form has little, if any, enzyme activity, usually 2% or less of normal activity. Symptoms are present in neonates (Strauss, Puffenberger and Morton,
The BCKDHA gene causes MSUD Type Ia due to the mutation in the E1α subunit, BCKDHB causes Type Ib due to the mutation in the E1ᵦ subunit, and DBT causes Type II due to defect in the E2 subunit (Strauss, Puffenberger and Morton, 2006). Mutations in these genes result in decreased or absent activity of the human branched-chain α-keto acid dehydrogenase complex (BCKAD) enzymes, consisting of subunits E1α, β, E2 and E3. …show more content…
If an individual inherits one normal gene and one mutated gene, the person will be a carrier for MSUD. The risk for two carrier parents to both pass the mutated gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females according to the National Organization for Rare Disorders (NORD.
Parents who are close relatives have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with MSUD. For example, there is a much higher prevalence in the Amish community in Pennsylvania due to the founder affect.
There are four subtypes of MSUD. They differ by their degree of severity, enzyme activity, and the age when the disease arises.
Classic MSUD is the most common and severe form of the condition. A person with this form has little, if any, enzyme activity, usually 2% or less of normal activity. Symptoms are present in neonates (Strauss, Puffenberger and Morton,