title: The first case in Asia of 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency (HSD10 disease) with atypical presentation.
abstract: 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (2M3HBD) deficiency (HSD10 disease) is a rare inborn error of metabolism, and <30 cases have been reported worldwide. This disorder is typically characterized by progressive neurodegenerative disease from 6 to 18 months of age. Here, we report the first patient with this disorder in Asia, with atypical clinical presentation. A 6-year-old boy, who had been well, presented with severe ketoacidosis following a 5-day history of gastroenteritis. Urinary organic acid analysis showed elevated excretion of 2-methyl-3-hydroxybutyrate and tiglylglycine. He was tentatively diagnosed with β-ketothiolase (T2) deficiency. However, repeated enzyme assays using lymphocytes showed normal T2 activity and no T2 mutation was found. Instead, a hemizygous c.460G>A (p.A154T) mutation was identified in the HSD17B10 gene. This mutation was not found in 258 alleles from Japanese subjects (controls). A normal level of the HSD17B10 protein was found by immunoblot analysis but no 2M3HBD enzyme activity was detected in enzyme assays using the patient's fibroblasts. These data confirmed that this patient was affected with HSD10 disease. He has had no neurological regression until now. His fibroblasts showed punctate and fragmented mitochondrial organization by MitoTracker staining and had relatively low respiratory chain complex IV activity to those of other complexes.
authors.affiliation: 1] Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan [2] Medical Information Sciences Division, United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukao
authors.affiliation: Department of General Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Akiba
authors.affiliation: Department of Endocrinology and Metabolism, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan.
authors.forename: Nobuki
authors.initials: N
authors.lastname: Kuwayama
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Morita
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Hori
authors.affiliation: Medical Information Sciences Division, United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Aoyama
authors.affiliation: Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Rajaram
authors.initials: R
authors.lastname: Venkatesan
authors.affiliation: Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Rik
authors.initials: R
authors.lastname: Wierenga
authors.affiliation: Department of Anatomy and Cell Biology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Yohsuke
authors.initials: Y
authors.lastname: Moriyama
authors.affiliation: Department of Anatomy and Cell Biology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Department of Anatomy and Cell Biology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Nobuteru
authors.initials: N
authors.lastname: Usuda
authors.affiliation: Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Murayama
authors.affiliation: 1] Department of Endocrinology and Metabolism, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan [2] Department of Pediatrics, Saitama Medical University, Moroyama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtake
authors.affiliation: Department of Pediatrics, Shimane University School of Medicine, Izumo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Health Science, Faculty of Medical Sciences, University of Fukui, Eiheiji-cho, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shigematsu
authors.affiliation: Department of Endocrinology and Metabolism, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Hasegawa
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000101:Acetyl-CoA C-Acetyltransferase / Q000172:deficiency* / Q000235:genetics; D001483:Base Sequence; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D002648:Child; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D020820:Dyskinesias; D005347:Fibroblasts / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D006885:Hydroxybutyrates / Q000652:urine; D015151:Immunoblotting; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D038901:X-Linked Intellectual Disability; D008928:Mitochondria / Q000378:metabolism; D008958:Models, Molecular; D017354:Point Mutation; D017434:Protein Structure, Tertiary
chemical_list: D006885:Hydroxybutyrates; C116917:acylcarnitine; C003603:tiglylglycine; C016579:2-methyl-3-hydroxybutyric acid; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human; D000101:Acetyl-CoA C-Acetyltransferase; D002331:Carnitine; D005998:Glycine