title: Neonatal mitochondrial hepatoencephalopathy caused by novel GFM1 mutations.
abstract: Disorders caused by defects in the mitochondrial translation system are clinically and genetically heterogeneous. The elongation phase of mitochondrial protein synthesis requires, among many other components, three nuclear-encoded elongation factors: EFTu (TUFM; 602389), EFTs (TSFM; 604723), and EFG1 (GFM1; 606639). Mutations have been identified in the genes encoding all three elongation factors, and they result in combined respiratory chain deficiencies and severe phenotypes with an early fatal outcome. So far, only eleven patients have been reported with mutations in GFM1. Here we describe an additional three patients with novel GFM1 mutations. Our results confirm the tissue-specific effect of GFM1 mutations, since we found only slightly decreased respiratory chain enzyme activities in muscle and fibroblasts, but a severe deficiency in the liver. Hence, a thorough biochemical evaluation is important to guide genetic investigation in patients suspected for a mitochondrial disorder.
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Ravn
authors.affiliation: Department of Clinical Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark.
authors.forename: Bitten
authors.initials: B
authors.lastname: Schönewolf-Greulich
authors.affiliation: Pediatrics Department, Herning Hospital, Herning, Denmark.
authors.forename: Rikke M
authors.initials: RM
authors.lastname: Hansen
authors.affiliation: Pediatrics Department, Nykoebing Falster Hospital, Nykoebing Falster, Denmark.
authors.forename: Anna-Helene
authors.initials: AH
authors.lastname: Bohr
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Duno
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Wibrand
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark.
authors.forename: Elsebet
authors.initials: E
authors.lastname: Ostergaard
keywords: CS, citrate synthase; EFG1 (GFM1, 606639); Mitochondrial disorder; Neonatal mitochondrial hepatoencephalopathy; OXPHOS, oxidative phosphorylation; RC, respiratory chain