title: Long-term survival in a child with severe encephalopathy, multiple respiratory chain deficiency and GFM1 mutations.
abstract: BACKGROUND
  Mitochondrial diseases due to deficiencies in the mitochondrial oxidative phosphorylation system (OXPHOS) can be associated with nuclear genes involved in mitochondrial translation, causing heterogeneous early onset and often fatal phenotypes.
  
  
  METHODS
  The authors describe the clinical features and diagnostic workup of an infant who presented with an early onset severe encephalopathy, spastic-dystonic tetraparesis, failure to thrive, seizures and persistent lactic acidemia. Brain imaging revealed thinning of the corpus callosum and diffuse alteration of white matter signal. Genetic investigation confirmed two novel mutations in the GFM1 gene, encoding the mitochondrial translation elongation factor G1 (mtEFG1), resulting in combined deficiencies of OXPHOS.
  
  
  CONCLUSIONS
  The patient shares multiple clinical, laboratory and radiological similarities with the 11 reported patients with mutations involving this gene, but presents with a stable clinical course without metabolic decompensations, rather than a rapidly progressive fatal course. Defects in GFM1 gene confer high susceptibility to neurologic or hepatic dysfunction and this is, to the best of our knowledge, the first described patient who has survived beyond early childhood. Reporting of such cases is essential so as to delineate the key clinical and neuroradiological features of this disease and provide a more comprehensive view of its prognosis.
authors: Serviço de Pediatria, Centro Hospitalar de Leiria, Hospital de Santo André Leiria, Portugal ; Neuromuscular Unit, Neuropaediatrics Department, Hospital Sant Joan de Déu Barcelona, Spain.
authors: Sara
authors: S
authors: Brito
authors: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University Newcastle upon Tyne, UK.
authors: Kyle
authors: K
authors: Thompson
authors: Neuromuscular Unit, Neuropaediatrics Department, Hospital Sant Joan de Déu Barcelona, Spain ; Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III Barcelona, Spain.
authors: Jaume
authors: J
authors: Campistol
authors: Neuromuscular Unit, Neuropaediatrics Department, Hospital Sant Joan de Déu Barcelona, Spain.
authors: Jaime
authors: J
authors: Colomer
authors: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University Newcastle upon Tyne, UK.
authors: Steven A
authors: SA
authors: Hardy
authors: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University Newcastle upon Tyne, UK.
authors: Langping
authors: L
authors: He
authors: Diagnosis and Treatment Unit for Inborn Errors of Metabolism, Hospital Clínico Universitario de Santiago de Compostela La Coruña, Spain.
authors: Ana
authors: A
authors: Fernández-Marmiesse
authors: Progenika Biopharma a Grifols Company Derio, Spain.
authors: Lourdes
authors: L
authors: Palacios
authors: Pathology Department, Hospital Sant Joan de Déu Esplugues Barcelona, Spain.
authors: Cristina
authors: C
authors: Jou
authors: Neuromuscular Unit, Neuropaediatrics Department, Hospital Sant Joan de Déu Barcelona, Spain ; Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III Barcelona, Spain.
authors: Cecilia
authors: C
authors: Jiménez-Mallebrera
authors: Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III Barcelona, Spain ; Biochemical, Genetics and Rett Unit, Laboratory Department, Hospital Sant Joan de Déu Esplugues Barcelona, Spain.
authors: Judith
authors: J
authors: Armstrong
authors: Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III Barcelona, Spain ; Biochemical Department, Hospital Sant Joan de Déu Esplugues Barcelona, Spain.
authors: Raquel
authors: R
authors: Montero
authors: Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III Barcelona, Spain ; Biochemical Department, Hospital Sant Joan de Déu Esplugues Barcelona, Spain.
authors: Rafael
authors: R
authors: Artuch
authors: Cluster of Excellence: Cellular Stress Responses in Aging-Associated Diseases (CECAD), Institute for Genetics, University of Cologne Cologne, Germany.
authors: Christin
authors: C
authors: Tischner
authors: Cluster of Excellence: Cellular Stress Responses in Aging-Associated Diseases (CECAD), Institute for Genetics, University of Cologne Cologne, Germany ; German Network for Mitochondrial Disorders (mitoNET) Munich, Germany.
authors: Tina
authors: T
authors: Wenz
authors: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University Newcastle upon Tyne, UK.
authors: Robert
authors: R
authors: McFarland
authors: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University Newcastle upon Tyne, UK.
authors: Robert W
authors: RW
authors: Taylor
keywords: GFM1; brain MRI; encephalopathy; mitochondrial disorders; mtEFG1