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Front Genet. 2015 Mar 23;6:102. doi: 10.3389/fgene.2015.00102. eCollection 2015.

Long-term survival in a child with severe encephalopathy, multiple respiratory chain deficiency and GFM1 mutations.

Author information

1
Serviço de Pediatria, Centro Hospitalar de Leiria, Hospital de Santo André Leiria, Portugal ; Neuromuscular Unit, Neuropaediatrics Department, Hospital Sant Joan de Déu Barcelona, Spain.
2
Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University Newcastle upon Tyne, UK.
3
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.
4
Neuromuscular Unit, Neuropaediatrics Department, Hospital Sant Joan de Déu Barcelona, Spain.
5
Diagnosis and Treatment Unit for Inborn Errors of Metabolism, Hospital Clínico Universitario de Santiago de Compostela La Coruña, Spain.
6
Progenika Biopharma a Grifols Company Derio, Spain.
7
Pathology Department, Hospital Sant Joan de Déu Esplugues Barcelona, Spain.
8
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.
9
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.
10
Cluster of Excellence: Cellular Stress Responses in Aging-Associated Diseases (CECAD), Institute for Genetics, University of Cologne Cologne, Germany.
11
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.

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.

CASE REPORT:

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.

DISCUSSION:

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.

KEYWORDS:

GFM1; brain MRI; encephalopathy; mitochondrial disorders; mtEFG1

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