title: Succinic Semialdehyde Dehydrogenase Deficiency in a Chinese Boy: A Novel ALDH5A1 Mutation With Severe Phenotype.
abstract: Succinic semialdehyde dehydrogenase deficiency is a rare autosomal recessive disorder affecting catabolism of the neurotransmitter gamma-aminobutyric acid (GABA), with a wide range of clinical phenotype. We report a Malaysian Chinese boy with a severe early onset phenotype due to a previously unreported mutation. Urine organic acid chromatogram revealed elevated 4-hydroxybutyric acid. Magnetic resonance imaging (MRI) of the brain demonstrated cerebral atrophy with atypical putaminal involvement. Molecular genetic analysis showed a novel homozygous 3-bp deletion at the ALDH5A1 gene c.1501_1503del (p.Glu501del). Both parents were confirmed to be heterozygotes for the p.Glu501del mutation. The clinical course was complicated by the development of subdural hemorrhage probably as a result of rocking the child to sleep for erratic sleep-wake cycles. This case illustrates the need to recognize that trivial or unintentional shaking of such children, especially in the presence of cerebral atrophy, can lead to subdural hemorrhage.
authors.affiliation: Department of Paediatrics, Faculty of Medicine, University Malaya, Malaysia taycheegeap@um.edu.my.
authors.forename: Chee Geap
authors.initials: CG
authors.lastname: Tay
authors.affiliation: Department of Paediatrics, Faculty of Medicine, University Malaya, Malaysia University of Malaya Cancer Research Institute, University Malaya, Malaysia.
authors.forename: Hany
authors.initials: H
authors.lastname: Ariffin
authors.affiliation: Department of Paediatrics, Faculty of Medicine, University Malaya, Malaysia Department of Metabolic Medicine, Sheffield Children's Hospital, NHS Foundation Trust, Western Bank, Sheffield, United Kingdom.
authors.forename: Sufin
authors.initials: S
authors.lastname: Yap
authors.affiliation: Department of Biomedical Imaging, University Malaya Research Imaging Centre, University Malaya, Malaysia.
authors.forename: Kartini
authors.initials: K
authors.lastname: Rahmat
authors.affiliation: Department of Pathology, Faculty of Medicine, University Malaya, Malaysia.
authors.forename: Pavai
authors.initials: P
authors.lastname: Sthaneshwar
authors.affiliation: Department of Paediatrics, Faculty of Medicine, University Malaya, Malaysia.
authors.forename: Lai Choo
authors.initials: LC
authors.lastname: Ong
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D044466:Asian People / Q000235:genetics; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002681:China; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D004569:Electroencephalography; D005500:Follow-Up Studies; D006801:Humans; D007214:Indonesia / Q000208:ethnology; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010290:Parents; D010641:Phenotype; D050644:Succinate-Semialdehyde Dehydrogenase / Q000172:deficiency* / Q000235:genetics
chemical_list: C493643:ALDH5A1 protein, human; D050644:Succinate-Semialdehyde Dehydrogenase
keywords:   ALDH5A1 gene; subdural hemorrhage; succinic semialdehyde dehydrogenase deficiency