[Updated 2013 May 9]. Maple Syrup Urine Disease. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.
What is Maple Syrup Urine Disease?
Maple syrup urine disease (MSUD) is an inherited metabolic disorder characterized by acidosis and sweet odor in the urine. Acidosis refers to excessive acid in bloodstream, resulting from inability to break down certain amino acids properly in the body. The signs and symptoms of this disorder include poor appetite, irritability, lethargy (lack of energy), developmental delay and a distinctive maple sugar odor in the body fluids such as sweat and urine. If left untreated, it can cause complications such as seizures, neurological damages or other life-threatening conditions. There are four clinically distinguishable forms of Maple syrup urine disease, each differ by severity, age of onset and the amount of functional enzyme. 1. Classic form This is the most severe and commonly observed form of Maple syrup urine disease. The age of onset is at birth. There is very little functional enzyme present in this form in this form of disease. 2. Intermediate form This form of Maple syrup urine disease is rare. The age of onset can vary and can range from approximately 5 months to 7 years of age. There is slightly more functional enzyme activity and symptoms of this form are less severe compared to the classic form. 3. Intermittent form This is a mild form of the disorder where physical and intellectual development is not interfered. There is more significant functional enzyme present and symptoms emerge at 1-2 years of age, as they start to consume more protein at this age. Proteins and amino acids are usually fairly well tolerated when these affected children are healthy, but they can develop symptoms of the disease during infections, stressful situations or after abnormal increase in protein intake. 4. Thiamine-responsive form This is also a rare form of the disorder, with age of onset occurring after infancy. Unlike the other forms mentioned above, symptoms for this form of Maple syrup urine disease can actually be improved with large doses of thiamine (vitamin B1). Maple syrup urine disease is caused by genetic mutations in the BCKDHA, BCKDHB and DBT genes, which together encode for proteins that make up the BCKAD (Branched-Chain alpha-KetoAcid Dehydrogenase) complex. This protein complex is involved in the normal breakdown of three amino acids (leucine, isoleucine and valine), which are commonly found in foods rich in protein such as meats, eggs and milk. Mutations in any of these genes can totally or partially reduce the function of BCKAD. Mutations in the BCKDHA gene gives rise to a defective alpha subunit of the BCKAD complex, and causes Maple syrup urine disease type 1A. Mutations in the BCKDHB gene gives rise to a defective beta subunit of the BCKAD complex, which causes Maple syrup urine disease type 1B. These mutations can interfere with the normal function of the BCKAD complex, which prevents the normal breakdown of leucine, isoleucine and valine, leading to accumulation of amino acids and byproducts in the body. Excessive buildups of these amino acids are toxic to cells and tissue, leading to the neurological damage and other serious complications associated with Maple syrup urine disease. References: Edelmann L, Wasserstein MP, Kornreich R, Sansaricq C, Snyderman SE, Diaz GA (2001). Maple Syrup Urine Disease: Identification and Carrier-Frequency Determination of a Novel Founder Mutation in the Ashkenazi Jewish Population. American Journal of Human Genetics. 69(4): 863-868. Jose CP, Ferreira MD, Schreiber-Agus N, Carter SM, Klugman S, MDa, Gregg AR, Gross SJ (2014). Carrier testing for Ashkenazi Jewish disorders in the prenatal setting: navigating the genetic maze. American Journal of Obstetrics and Gynecology. 211(3): 197-204. Strauss KA, Puffenberger EG, Morton DH (2006)DNA In the News2017-04-06T21:06:11+00:00