2012 Fiscal Year Final Research Report

Familial hyperleucinemia with normal branched-chain α-ketoacid dehydrogenase activity suggesting novel mechanism of thiamin-responsive maple syrup urine disease

Research Project

Project/Area Number	22591131
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Pediatrics
Research Institution	Hiroshima University
Principal Investigator	TAJIMA Go 広島大学, 大学院・医歯薬保健学研究院, 助教 (00432716)
Research Collaborator	OKADA Satoshi 広島大学, 病院(医), 病院助教 (80457241) TSUMURA Miyuki 広島大学, 大学院・医歯薬保健学研究院, 研究員 (80646274) KAGAWA Reiko 広島大学, 大学院・医歯薬保健学研究院, 大学院生 UTSUNOMIYA Akari 広島大学, 大学院・医歯薬保健学研究院, 大学院生 MIZOGUCHI Yoko 広島大学, 大学院・医歯薬保健学研究院, 大学院生
Project Period (FY)	2010 – 2012
Keywords	小児代謝・栄養学 / メープルシロップ尿症 / 分枝鎖α-ケト酸脱水素酵素複合体 / 分枝鎖α-ケト酸脱水素酵素キナーゼ(BCKDK) / 常染色体優性遺伝
Research Abstract	We performed genetic analysis of two siblings showing persistent hyperleucinemia since newborn period in spite of normal levels of branched-chain α-ketoacid dehydrogenase (BCKD) activity, and detected a heterozygous missense basal substitution in BCKD kinase (BCKDK) gene that derived from their father. As BCKDK inactivates BCKD complex by phosphorylation of E1αsubunit, this family suggests a novel autosomal-dominant subtype of maple syrup urine disease caused by a gain-of-function mutation of BCKDK.