The toxicity is the result of damaging effects of leucine on the brain accompanied by severe ketoacidosis caused by accumulation of the three branched-chain ketoacids (BCKAs). Maple syrup urine disease derives its name from the characteristic odor of the urine. (For more information on this disorder, choose “methylmalonic acidemia” as your search term in the Rare Disease Database. Helpful, trusted answers from doctors: Dr. Peck on maple syrup disease in adults: Infants with msud lack an enzyme to break down Amino Acids (proteins) in their diet, so the acids accumulate in their blood and tissues and become toxic, causing sweet-smelling urine, ear wax, etc-hence the name-but also brain damage. The onset and symptoms of intermediate MSUD may be neonatal, but the majority of children are diagnosed between the ages of five months and seven years. Introduction. Variant maple syrup urine disease (MSUD) – the entire spectrum. Once in hospital, your baby can be monitored and treated with fluids given directly into a vein (intravenous fluids). Metabolic acidosis is not a feature. Artificially-made (synthetic) formulas are available that provide all the nutrients necessary for proper growth and development, but lack leucine, isoleucine and valine. Mov Disord. Various techniques have been used to reduce plasma leucine levels including dialysis or a process in which blood is removed from the body and passed through a filter before being returned to the body (hemofiltration). Some individuals may develop increased pressure in the skull (intracranial hypertension), which causes painful headaches that are sometimes associated with nausea and vomiting. The disease prevents your body from breaking down certain amino acids. Maple Syrup Urine Disease. Intermittent forms of the disease may present later (5 months to 2 years of age) and can be precipitated by concomitant infection or a high protein intake 8. 1999;158 Suppl 2:S60-64. If you're a carrier of the affected genes and have a baby with a partner who's also a carrier, your baby has: Although it's not possible to prevent MSUD, it's important to let your midwife and doctor know if you have a family history of the condition. … Children diagnosed with MSUD are first referred to a specialist metabolic dietitian and given a low-protein diet. Protein is needed by the body to function normally. Additional complications with classic MSUD include generalized loss of bone mass (osteoporosis) that may predispose to fractures, and inflammation of the pancreas (pancreatitis). Maple syrup urine disease: Deficiency of an enzyme called BCKD causes buildup of amino acids in the body. In the end, central neurologic function fails with respiratory failure and death. Maple syrup urine disease: A very rare inherited metabolic disorder involving abnormal metabolism of branched chain amino acids (leucine, isoleucine and valine) and resulting in severe illness which generally leads to death if not treated. Even if affected individuals follow the specialized diet strictly, the risk of metabolic crisis always remains. Mol Genet Metab 82: 69–75. Available at: http://www.emedicine.com/ped/topic1368.htm Accessed June 3, 2020. maple syrup urine disease in adults. However, its administration is ineffective in cases of gastric intolerance and some adult patients refuse enteral feeding via a nasogastric tube. ... Genetic disorder: Maple syrup urine disease is an inherited genetic disorder of protein breakdown. Protein-restriction must start as soon as possible after birth to promote proper growth and development. Maple syrup urine disease (MSUD) is a genetic disorder and is caused by changes or mutations in some genes that signal the body to produce certain enzymes necessary for digestion and metabolism. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. GeneReviews® [Internet]. The toxicity of these amino acids is restricted to leucine; indeed, extra valine and isoleucine are often given during treatment. Without treatment, severe, life-threatening symptoms can develop, including seizures (fits) or falling into a coma. Available at: http://omim.org/entry/248600. TREATMENT of the episode of acute metabolic decompensation in maple syrup urine disease (MSUD) is a medical emergency. The genetic defect that produces MSUD results in a defect in the enzyme called branched-chain alpha-keto acid dehydrogenase (BCKD), which is necessary for the breakdown of the amino acids leucine, isoleucine, and valine. It should be noted that Intermediate MSUD patients are susceptible to the same degree of neurologic complications and extreme acidosis as those with classic MSUD. Rashed MS, Rahbeeni Z, Ozand PT. This is derived from one of the BCKA organic acids derived from its respective BCAA that accumulate as the disorder spirals out of control. This means that ANY method to increase calories, to reduce protein catabolism (for energy needs) may be helpful. Background: In MSUD, dietary treatment aims at the protection of the brain from functional disturbances and structural damage by keeping the branched-chain amino acids in plasma permanently in the near-normal range. Menu Online Mendelian Inheritance in Man (OMIM). There is considerable genetic heterogeneity due to various mutations that occur in the E1 alpha, E1 beta, E2 and E3 loci of the BCKAD complex. 3. Affected children must be regularly monitored to ensure that their diet is adequate and that amino acid levels remain within acceptable normal ranges. Eur J Pediatr. ), Glycine encephalopathy is an inborn error of metabolism characterized by the accumulation of large amounts of the amino acid glycine in blood and, particularly, in the cerebrospinal fluid (CSF). Baltimore. 2002;109:999-1008. The symptoms usually arise during early infancy, but may even remain occult until adulthood. An increasing catabolic rate can occur insidiously or may develop rapidly during any metabolic stress, including infection, even if very mild, psychological or physical stress, trauma or fasting. During anabolism, amino acids and other compounds are synthesized to form new muscle and other proteins as well as a huge variety of other compounds. Mutations in these genes result in absent or decreased activity of human branched-chain alpha-ketoacid dehydrogenase complex (BCKAD) enzymes. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Tandem mass spectrometry, an advanced newborn screening test that screens for more than 40 different disorders through one blood sample, has aided in the diagnosis of MSUD. One of the characteristic symptoms of MSUD is sweet-smelling urine, which gives the condition its name. No individuals with thiamine-responsive MSUD have been treated solely with thiamine – most follow a combination of thiamine with a partially-restricted protein diet. The genetic change (mutation) responsible for MSUD is passed on by the parents, who usually do not have any symptoms of the condition. Normally, our bodies break down protein foods such as … These analyses must be performed in a laboratory that is experienced in the relevant techniques. Movement disorders in adult surviving patients with maple syrup urine disease. If untreated, maple syrup urine disease can lead to seizures, coma, and death. Maple syrup urine disease (MSUD, MIM #248600) also known as branched-chain ketoaciduria, is a disorder affecting the aliphatic or branched-chain amino acids. Newborn screening for MSUD is performed throughout the US and in many other countries so that most such infants are detected through these programs. Intermittent maple syrup urine disease is a milder form of the disease. Copyright ©2020 NORD - National Organization for Rare Disorders, Inc. All rights reserved. Individuals with this type have a greater level of enzyme activity (approximately 8 to 15% of normal) and often do not have symptoms until 12 to 24 months of age, usually as a result of an illness or surge in protein intake. These enzymes are responsible for breaking down the branched chain amino acids leucine, isoleucine, and valine that are in all proteins. This contains all the vitamins, minerals and other amino acids your baby needs. 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