Maple Syrup Urine Disease

   Maple Syrup Urine Disease, MSUD, is also known as BCKD deficiency, branched-chain alpha-ketoacid dehydrogenase deficiency, ketoacidemia, branched-chain ketoaciduria

and branched-chain ketouria 1. MSUD is a metabolism disorder where the body is unable to break down certain parts of proteins. It was first characterized by pediatrician John Menkes in 1954, and got its name from the odor of the urine produced by individuals with the disease. MSUD occurs in an autosomal recessive pattern, which means both parents must be carriers to pass the disease.
   The cause of MSUD is a defect in any of the 6 subunits of the BCKD protein complex. The most common defect is caused by the mutation in a gene on chromosome 19 that encodes the alpha subunit of the BCKD complex. The process works like this: the body digests protein, leaving amino acids. Enzymes break down amino acids to maintain body functions. When the necessary enzymes are missing or defective, amino acids and their bi-products, called keto acids, collect in the body. MSUD causes the body to not have the enzymes from the group BCKAD complex, which processes leucine, isoleucine, and valine. These amino acids are found in high protein foods such as milk, eggs, and meat.
   There are four subtypes of MSUD:
Classic MSUD is the most common. The patient will have little if any enzyme action, less than 2%. It is also the most severe form, and signs show up in newborns within the first few days after birth.
Intermediate MSUD is a rare form but a version of classic. The symptoms and age of onset vary greatly. There is a higher level of enzyme activity, around 3-8%.
Intermittent MSUD does not interfere with normal physical and intellectual growth and development. It is a milder form of classic, and has about an 8-15% normal enzyme activity.
Thiamine-responsive MSUD is a rare form that improves with large doses of thiamine as well as Vitamin B1. Signs occur during infancy.
   The symptoms of MSUD in infants include: tiredness, trouble sucking while feeding, irritability, loss of appetite, sleeping longer more often, weight loss, high pitched cry, and developmental delays. The symptoms of adults include: loss of appetite, avoiding food, vomiting, seizures, and lethargy. Some of the more severe symptoms are swelling of the brain or lack of blood flow to the brain, coma, and metabolic acidosis. The most common symptom is urine that has an odor of maple syrup.
   Though there is no know cure for MSUD, there are many ways to treat it. The most common treatment is a dietary restriction plan set up by your doctor or genetic counselor. Newborn screening is usually available to test for MSUD. Sometimes, adding thiamine or Vitamin B1 can help.  It has also been proven that a liver transplant to someone with liver failure due to MSUD can eliminate the issue all together. If left untreated, MSUD can cause the rapid degeneration of brain cells, and eventually, lead to death.
   The most common support group is the MSUD Family Support Group. The biggest supporter or research for MSUD is the Genetic and Rare Diseases Information Center.