![]() These amino acids are also substrates for energy production via succinyl-CoA and acetoacetate. They are the precursor for fatty acids and cholesterol synthesis through acetyl-CoA. BCAAs, as a group, are both ketogenic and glucogenic. The end products of leucine catabolism are acetyl-CoA and acetoacetate. These reactions generate the respective branched-chain acyl-CoAs that are further metabolized via separate pathways. BCKAs synthesized in the cytosol are translocated by the specific BCKA transporter into mitochondria, where oxidative decarboxylation of the three BCKAs is catalyzed by the single BCKD multienzyme complex. Α-ketoisocaproate (KIC) from leucine, α-keto-β-methylvalerate (KMV) from isoleucine, and α-ketoisovalerate (KIV) from valine. Inside the cell, BCAAs undergo reversible transamination by the cytosolic or mitochondrial isoforms of the branched-chain amino acid aminotransferase (BCAT) in the respective compartment to produce the BCKAs The catabolic pathways for BCAAs begin with the transport of these amino acids into cells by the system L transporter located in the cytosolic membrane. The BCAAs comprise about 35 percent of the indispensable amino acids in muscle, and 40 percent of the performed amino acids required by mammals. In the inbred Old Order Mennonite population of Lancaster and Lebanon Counties, Pennsylvania, MSUD occurs in approximately 1 in 176 newborns. The worldwide frequency based on routine screening data from 26.8 million newborns is approximately 1 in 185,000. MSUD is an autosomal recessive metabolic disorder of panethnic distribution. An animal model in Polled Hereford calves has been described. This is the result of E3 being a common component of the three mitochondrial multienzymes. The E3-deficient MSUD presents a combined deficiency of BCKD, pyruvate dehydrogenase, and α-ketoglutarate dehydrogenase complexes. Activity of the BCKD complex in skin fibroblasts or lymphoblast cultures is reduced, and ranges from less than 2 percent of normal in the classic form to 30 percent of normal in the variant forms. The presence of alloisoleucine is diagnostic of MSUD. The levels of the BCAAs, particularly leucine, are greatly increased in plasma and urine. ![]() Variant forms of MSUD generally have the initial symptoms by 2 years of age. Classic MSUD has a neonatal onset of encephalopathy and is the most severe and most common form. Based on the clinical presentation and biochemical responses to thiamine administration, MSUD patients can be divided into five phenotypes: classic, intermediate, intermittent, thiamine-responsive, and dihydrolipoyl dehydrogenase (E3)-deficient. This metabolic block results in the accumulation of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine, and the corresponding branched-chain α-keto acids (BCKAs). ![]() We sincerely appreciate any donations you may choose to make.Maple syrup urine disease (MSUD) or branched-chain ketoaciduria is caused by a deficiency in activity of the branched-chain α-keto acid dehydrogenase (BCKD) complex. We rely on donations to fund our newsletters, biennial symposium, our research program and other activities. Want to help? Assistance is always needed to connect and support MSUD families, prepare our newsletters, assist in the biennial symposium, participate in advocacy events, and other activities.īe A Volunteer Support MSUD Research and Other Services Also, see our archive of past newsletters dating back to 1988. Join our newsletter list to receive our semi-annual newsletters as they are available. ![]() Click below if you’d like to help and to donate. Volunteers are always needed and your generous donations help us do our work. We are 100% volunteer run and funded almost entirely by donations.įamilies with newly diagnosed MSUD children can call members of the Board of Directors (see “Contacts”) to learn more about MSUD and the MSUD Family Support Group. The MSUD Family Support Group is a tax exempt 501(c)3 organization. Th e MSUD Family Support Group Is An All-Volunteer Organization
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