title: Clinical and molecular investigations of Japanese cases of glutaric acidemia type 2.
abstract: Glutaric acidemia type 2 (GA2) is an autosomal recessive disorder resulting from a deficiency of electron transfer flavoprotein (ETF) or ETF dehydrogenase (ETFDH) that manifests from most severe neonatal to late-onset forms. However, the genetic defect responsible for the disease and clinical severity is not well-characterized. In order to understand the relationship between the phenotype and genetic defect, we investigated the clinical and molecular features of 15 Japanese patients, including 4 previously reported cases. Three patients had the neonatal form and 8 patients had the late-onset form, 1 of whom presented an extremely mild phenotype. Immunoblot analysis showed that either ETFalpha, ETFbeta, or ETFDH was significantly reduced or absent in all patients. However, no specific enzyme deficiency predominated, and there were no associations with the clinical severity. Genetic analyses identified 15 mutations including non-sense, missense, splice site mutations, and small deletions, in ETFA, ETFB and ETFDH genes. Although almost all mutations were unique to Japanese patients and no common mutations were found, some of them appeared to be associated with a specific phenotype. Our results suggest that clinical and mutational spectrums of Japanese GA2 patients are heterogeneous and that genetic diagnoses may help to predict a prognosis and provide more accurate diagnostic information for patients and families with GA2.
authors.affiliation: Department of Pediatrics, Shimane University School of Medicine, Izumo, Shimane 693-8501, Japan. yukana@med.shimane-u.ac.jp
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yotsumoto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukuda
authors.forename: Hironori
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Endo
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukao
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
mesh_terms: D002478:Cells, Cultured; D044927:Electron-Transferring Flavoproteins / Q000235:genetics; D005260:Female; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics; D007564:Japan; D008297:Male; D054069:Multiple Acyl Coenzyme A Dehydrogenase Deficiency / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D010641:Phenotype
chemical_list: D044927:Electron-Transferring Flavoproteins; D007506:Iron-Sulfur Proteins; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase