Maple syrup urine disease: a possible biochemical basis for the clinical heterogeneity

✍ Scribed by Yasuhiro Indo; Izumi Akaboshi; Yoshitaka Nobukuni; Fumio Endo; Ichiro Matsuda

• Publisher: Springer
• Year: 1988
• Tongue: English
• Weight: 653 KB
• Volume: 80
• Category: Article
• ISSN: 0340-6717
• DOI: 10.1007/bf00451447

✦ Synopsis

Nine patients with maple syrup urine disease (MSUD), of whom eight were detected by mass-screening of neonates for inherited metabolic desease, were studied to determine possible relationships between clinical features and properties of the branched-chain c~-keto acid dehydrogenase complex (BCKDH) in cultured lymphoblastoid cells. Based on their tolerance for leucine and on the clinical manifestations observed after 2 years of age, most could be classified into three types; classical (tolerate less than 600 mg of leucine per day, N = 2), intermediate (N = 3) and intermittent (N = 3) types. In the other patient two of these three phenotypes were present. The BCKDH activities measured at a lower c~ketoisovaleric acid concentration (0.054raM) were 0.026 ___ 0.015 in classical, 0.118 _+ 0.016 in intermediate and 0.625 _ 0.139 in intermittent types and 7.052 _+ 0.779 (nmol/h per milligram of protein) in two controls, respectively; the differences being statistically significant (P < 0.01, classical vs intermediate types; P< 0.01, intermediate vs intermittent types; P < 0.01, intermittent vs control). Kinetic and immunochcmical analyses of the BCKDH revealed that, although there are a few exceptions, classical, intermediate and intermittent types correspond to the enzyme properties of sigmoidal kinetics with E~ subunit deficiency, near-sigmoidal kinetics with E~ subunit deficiency and hyperbolic kinetics with E2 subunit deficiency of the BCKDH, respectively.