Maple Syrup Urine Disease: Type 1B

Maple syrup urine disease (MSUD) is an inherited disorder named for the maple syrup or burned sugar smell from affected infants' urine and earwax. This disease is caused by lack of the enzyme (BCKAD) needed to process certain amino acids found in all foods containing protein. These amino acids and other substances build up in the blood and can cause serious damage to the brain. Infants affected by the most severe form of MSUD show poor feeding, vomiting, and lack of energy within the first several days of life. If untreated, death can occur within the first few months after birth. With early and lifelong treatment involving a special diet, individuals may develop normally and live a normal life span. However, despite careful treatment, there is an increased risk of learning problems, mental disability, and death. Infants with less severe forms of MSUD may appear normal at birth and have normal growth, but careful life and diet management is still critical to lifelong survival. MSUD is a condition that is tested for in states that have expanded newborn screening. MSUD type 1B is caused by pathogenic variants in the BCKDHB gene, making up the beta subunit of the BCKAD enzyme.

MSUD type 1B 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.

There are generally no signs or symptoms associated with being a carrier for MSUD. Carriers are at an increased risk of having a child affected with MSUD. Testing of reproductive partners is recommended for carriers of MSUD.

MSUD is a rare disorder, occurring in 1 in 185,000 live births in the general population. The disorder is much more frequent in children of Mennonite populations, occurring about 1 in 380 newborns. In the Ashkenazi Jewish population, about 1 in 50,000 newborns are born with MSUD. MSUD type 1B makes up about one third of all MSUD cases.

Genetics Home Reference: Maple syrup urine disease (MSUD) (http://ghr.nlm.nih.gov/)
Genetic Alliance: Maple syrup urine disease (http://www.diseaseinfosearch.org/)

OMIM [Maple syrup urine disease (MSUD): 248600] (http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: Maple syrup urnine disease (MSUD) (http://www.ncbi.nlm.nih.gov/books/NBK1116/)

• Full gene sequencing