Maple Syrup Urine Disease (MSUD)

Maple Syrup Urine Disease (MSUD) is a recessive metabolism disorder that causessevere neurological symptoms and causes fatal swelling of the brain in infants. This devastating disease is caused by a mutation in one of three genes, BCKDHA, BCKDHB and DBT, that forms a protein complex that breaks down large amino acids, branched-chain amino acids (BCAA’s) essential for life. Due to mutations in one of these genes results in a dysfunctional protein that can no longer break down these BCAA’s and thus causes toxic accumulation in cells throughout the body. Individuals with MSUD have poor feeding behaviors, lethargy, irritability, central respiratory failure, abnormal skeletal muscle function and neurological and cognitive abnormalities. If not diagnosed immediately at birth, children will develop highly fatal cerebral edema (brain swelling) and subsequent coma in just a few days. This scenario can potentially be prevented by careful dietary regulation consisting of BCAA-free diet, but it will not fully prevent MSUD crises (cerebral edema) nor development of behavioral and cognitive abnormalities like low IQ and psychiatric disorders. Liver transplantation is a potential therapeutic strategy for MSUD but has major disadvantages, such as shortage of available organs, high inherent risks, and it does not alleviate behavioral/cognitive deficits. Ultimately, the quality of life of MSUD patients remains low and our goal in this lab is to develop a gene therapy that can help treat this devastating disease. The Gray-Edwards lab is working closely with the Clinic for Special Children in Strasburg, Pennsylvania on this project.

Cow model of MSUD

A cow model of MSUD was first reported in Indiana. These cows have many of the same disease features as seen in human patients, and our lab has acquired these animals to help further describe the disease as well as develop treatments for MSUD.