title: Clinical and molecular investigation in Chinese patients with glutaric aciduria type I.
abstract: Glutaric aciduria type I (GA-I) is a rare autosomal recessive metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase (GCDH), leading to an abnormal metabolism of lysine, hydroxylysine and tryptophan. It results in accumulations of glutaric acid, 3-hydroxyglutaric acid and glutaconic acid. Clinical features include the sudden onset of encephalopathy, hypotonia and macrocephaly usually before age 18months. Here we report five cases of GA-I confirmed with mutation analysis. GCDH gene mutations were identified in all five probands with GA-I. Three of them had compound heterozygous mutations and two had homozygous mutations. Mutations of two alleles (c.334G>T and IVS11-11A>G) were novel and both of them were confirmed to be splice site mutations by reverse transcription PCR.
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China.
authors.forename: Yanghui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China; Hunan Jiahui Genetics Hospital, 110 Xiangya Road, Changsha, Hunan 410078, China.
authors.forename: Haoxian
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China.
authors.forename: Ruiyu
authors.initials: R
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Mei
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China.
authors.forename: Xianda
authors.initials: X
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China; Hunan Jiahui Genetics Hospital, 110 Xiangya Road, Changsha, Hunan 410078, China. Electronic address: liangdesheng@sklmg.edu.cn.
authors.forename: Desheng
authors.initials: D
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China; Hunan Jiahui Genetics Hospital, 110 Xiangya Road, Changsha, Hunan 410078, China. Electronic address: wulingqian@sklmg.edu.cn.
authors.forename: Lingqian
authors.initials: L
authors.lastname: Wu
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001928:Brain Diseases, Metabolic / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005977:Glutarates / Q000378:metabolism; D050770:Glutaryl-CoA Dehydrogenase / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation
chemical_list: C108959:3-hydroxyglutaric acid; D005977:Glutarates; D050770:Glutaryl-CoA Dehydrogenase; C035736:glutaric acid
keywords: GCDH; Glutaric aciduria type I; Newborn screening; Splice site mutation