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7077671 
Journal Article 
Maple syrup urine disease (MSUD): Molecular defect and clinical management 
Matsuda, I; , 
1996 
CHINESE UNIV PRESS 
HONG KONG 
59-62 
Maple syrup urine disease (MSUD) is an autosomal recessive disease caused by a deficiency in any of the subunits (E1 alpha, E1 beta, E2) of the branched chain alpha-ketoacid dehydroxylase complex (BCKDH). Since 1977, 36 Japanese patients with MSUD were identified by mass screening. Six died and the other 30 were followed while on specially prescribed diets. Among the 15 patients that we had studied, 8 had the classic type (leucine tolerance <600 mg/day) and 7 the non-classic type (intermittent, intermediate). BCKDH activity was 1.4 +/- 1.7% in classic and 5.6 +/- 3.0% in non-classic cases. Complementation study and gene analysis showed that 7 (3 classic, 4 non-classic) had E1 alpha deficiency, 4 (all classic) E1 beta deficiency and 4 (2 classic, 2 non-classic) E2 deficiency. Only 2 identical mutant alleles were found in 2 families, one with E1 alpha (A209T) and the other with E1 beta (11 bp dell) deficiency. All others were heterogeneous. Western analysis showed that missense mutations in the highly conserved codon of BCKDH and pyruvate dehydrogenase complex in other species, such as R115W, T209A in E1( gene, and frame shift mutations generating early and downstream stop codon generally result in classic MSUD with a severe reduction in the associated subunits (E1 alpha + E1 beta or E2) of BCKDH. IQ or DQ was 69.0 +/- 16.7 in the classic and 93.9 +/- 10.7 in the non-classic MSUD patients. 
Lam, STS; Pang, CCP; 
962-201-765-7 
2nd Asian Pacific Regional Meeting of the International-Society-for-Neonatal-Screening 
HONG KONG, HONG KONG