Neonatal mitochondrial hepatoencephalopathy caused by novel GFM1 mutations

Kirstine Ravn; Bitten Schönewolf-Greulich; Rikke M Hansen; Anna-Helene Bohr; Morten Duno; Flemming Wibrand; Elsebet Ostergaard

doi:10.1016/j.ymgmr.2015.01.004

Neonatal mitochondrial hepatoencephalopathy caused by novel GFM1 mutations

Mol Genet Metab Rep. 2015 Feb 20:3:5-10. doi: 10.1016/j.ymgmr.2015.01.004. eCollection 2015 Jun.

Authors

Kirstine Ravn¹, Bitten Schönewolf-Greulich², Rikke M Hansen³, Anna-Helene Bohr⁴, Morten Duno¹, Flemming Wibrand¹, Elsebet Ostergaard¹

Affiliations

¹ Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark.
² Department of Clinical Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark.
³ Pediatrics Department, Herning Hospital, Herning, Denmark.
⁴ Pediatrics Department, Nykoebing Falster Hospital, Nykoebing Falster, Denmark.

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.

Keywords: CS, citrate synthase; EFG1 (GFM1, 606639); Mitochondrial disorder; Neonatal mitochondrial hepatoencephalopathy; OXPHOS, oxidative phosphorylation; RC, respiratory chain.