I came across this disease while taking my HESI practice exam today. I had never come across this disease prior to today. So I decided to look it up.
“MSUD is caused by a deficiency of the BCKD complex, which catalyses the decarboxylation of the alpha-keto acids of leucine, isoleucine, and valine to their respective branched-chain acyl-CoAs. These are further metabolized to yield acetyl-CoA, acetoacetate, and succinyl-CoA. Accumulation of these 3 amino acids and their corresponding keto acids leads to encephalopathy and progressive neurodegeneration in untreated infants.
The BCKD complex, which is associated with the inner mitochondrial membrane, has 3 different catalytic components (ie, E1, E2, E3) and 2 associated regulatory enzymes (ie, BCKD phosphatase, BCKD kinase). In addition, the E1 component consists of 2 distinct subunits (ie, E1 alpha, E1 beta) that form an alpha-2 beta-2 heterotetramer. The E3 component is associated with 2 additional alpha-ketoacid dehydrogenase complexes, namely pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase. Mutations in E1, E2, or E3 cause MSUD. No good genotype-phenotype correlation between molecular and clinical phenotypes is known, with the exemption of mutations in E2, which cause thiamine-responsive MSUD. Mutations in E3 cause additional deficiencies of pyruvate and alpha-ketoglutarate dehydrogenases.[6] Mutations in the regulatory enzymes have not been reported.
Accumulation of leucine in particular causes neurological symptoms, whereas elevation of plasma isoleucine is associated with the maple syrup odor. Leucine is rapidly transported across the blood-brain barrier and is metabolized to presumably yield glutamate and glutamine.” -emedicine
I found your blog through a Google alert for MSUD. My daughter has MSUD, and I blog about our experiences with it at http://www.ourtransplantjourney.net.
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