Maple syrup urine disease: a possible biochemical basis for the clinical heterogeneity.
Nine patients with maple syrup urine disease (MSUD), of whom eight were detected by mass-screening of neonates for inherited metabolic disease, were studied to determine possible relationships between clinical features and properties of the branched-chain alpha-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 alpha-ketoisovaleric acid concentration (0.054 mM) 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 less than 0.01, classical vs intermediate types; P less than 0.01, intermediate vs intermittent types; P less than 0.01, intermittent vs control). Kinetic and immunochemical 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 E1 beta subunit deficiency, near-sigmoidal kinetics with E1 beta subunit deficiency and hyperbolic kinetics with E2 subunit deficiency of the BCKDH, respectively.
Department of Pediatrics, Kumamoto University Medical School, Japan.
Y
Y
Indo
I
I
Akaboshi
Y
Y
Nobukuni
F
F
Endo
I
I
Matsuda
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D002460:Cell Line; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D007700:Kinetics; D007930:Leucine / Q000097:blood; D008297:Male; D008375:Maple Syrup Urine Disease / Q000235:genetics* / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*
D009097:Multienzyme Complexes; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D007930:Leucine