Abstract
Thiamine pyrophosphate (TPP) is a coenzyme of mammalian branched chain α-ketoacid dehydrogenase complex (BCKAD). We have previously reported the in vitro stabilizing effect of saturating quantities of TPP on this multienzyme complex (Arch. Biochem. and Biophys. 202:23, 1980). In this investigation, we study the in vivo response to thiamine of four children affected with Maple Syrup Urine Disease (MSUD), (CM, JP, TMc and VH). Fasting plasma levels of the branched chain amino acids, α-ketoacids and the BCKAD activity in peripheral leukocytes were measured before and during four weeks of 200mg thiamine P.O. per day while maintaining identical diets. TMc, VH and JP had significant falls in the mean blood values for all three branched chain amino acids (p<0.05). Corresponding decreases in plasma branched chain α-ketoacids occurred in TMc and JP, but not VH. CM exhibited no decrease in the measured parameters. The patients exhibiting a response (TMc, VH and JP) had measured BCKAD activity in their peripheral leukocytes ranging from 3-10% of normal controls, while CM had enzyme activity less than 1% of the normal controls. These results indicate that some patients with MSUD will respond to supraphysiological thiamine supplements and that the ability to respond is associated with residual enzyme activity present. The mechanism postulated for this response is stabilization of the BCKAD enzyme complex when TPP binding sites are occupied. (Supported by NIH Grants HD 08388 & CRC 00039).
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Elsas, L., Lubitz, D., Fernhoff, P. et al. 713 THIAMINE RESPONSIVE MAPLE SYRUP URINE DISEASE. Pediatr Res 15 (Suppl 4), 561 (1981). https://doi.org/10.1203/00006450-198104001-00736
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DOI: https://doi.org/10.1203/00006450-198104001-00736