Genetic mutation profile of isovaleric acidemia patients in Taiwan.
Isovaleric acidemia (IVA), a rare recessive autosomal disorder, is caused by isovaleryl-CoA dehydrogenase (IVD) deficiency. IVA may present with symptoms during the acute stage of severe metabolic acidosis, ketosis, vomiting, and altered mental status. With the help of newborn screening (NBS) by tandem mass spectrometry (MS/MS), IVA can now be diagnosed presymptomatically. According to statistic data, the incidence of IVA in Taiwan was about 1/365,000. In this study, six IVA patients from five families were investigated and followed-up clinically. As for the timing, two patients were found before MS technique introduced to Taiwan, the others were identified after MS/MS applied to NBS. The blood level of C5-carnitine in our patients was 7.43-18.96 microM (with upper limit in our laboratory <0.51 microM) and all of their urines contained raised amounts of 3-hydroxyisovaleric acid and isovalerylglycine. Molecular analysis of their IVD gene revealed six mutation profiles, among which the 149G-->A (Arg21His) and 1174 C-->T (Arg363Cys) mutations have been reported previously, while the other four mutations, 386A-->G (His100Arg), 347C-->T (Ser87Phe), 1007G-->A (Cys307Tyr) and 1199A-->G (Tyr371Cys), were first reported. Specially, we found 1199A-->G (Tyr371Cys) mutated was a common recurring missense mutation in our population (4 in 10 mutant alleles).
Lin
Wei-De
WD
Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
Wang
Chung-Hsing
CH
Lee
Cheng-Chung
CC
Lai
Chien-Chen
CC
Tsai
Yushin
Y
Tsai
Fuu-Jen
FJ
D000328:Adult; D002331:Carnitine / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D045782:Hemiterpenes; D006801:Humans; D007223:Infant; D050769:Isovaleryl-CoA Dehydrogenase / Q000235:genetics*; D008297:Male; D008661:Metabolism, Inborn Errors / Q000209:etiology / Q000235:genetics*; D009154:Mutation; D010421:Pentanoic Acids / Q000378:metabolism; D011110:Polymorphism, Genetic; D021241:Spectrometry, Mass, Electrospray Ionization; D013624:Taiwan
D045782:Hemiterpenes; D010421:Pentanoic Acids; C008216:isovaleric acid; D050769:Isovaleryl-CoA Dehydrogenase; D002331:Carnitine