Case study A mitochondrial tRNA Met mutation causing developmental delay, exercise intolerance and limb girdle phenotype with onset in early childhood Alfred Peter Born a,* , Morten Duno b , Jabin Rafiq c , Lotte Risom b , Flemming Wibrand b , Elsebet Østergaard b , John Vissing c a Paediatric Clinic, University of Copenhagen, Rigshospitalet, Denmark b Department of Clinical Genetics, University of Copenhagen, Rigshospitalet, Denmark c Neuromuscular Research Unit, University of Copenhagen, Rigshospitalet, Denmark article info Article history: Received 31 March 2014 Accepted 24 October 2014 Keywords: Mitochondrial tRNA Met mutation Limb-girdle muscle weakness Exercise intolerance Lactic acidosis abstract A 10-year-old girl presented with exercise intolerance, learning difficulty, and muscle weakness in a limb girdle distribution. She had delayed achievement of motor milestones and difficulties with social interaction at pre-school age. Muscle biopsy showed no myopathic or dystrophic features, but 90% COX negative fibres and ragged blue fibres. Respiratory chain enzyme analysis in muscle showed a combined deficiency and mito- chondrial DNA sequencing revealed the presence of an m.4450G>A mutation in the MT-TM gene encoding the tRNA for methionine. The mutation was only detected in mtDNA extracted from muscle and skin fibroblast, and could not be found in other tissues or in the mother. This is the second patient reported in the literature with a mitochondrial myop- athy due to a mt-tRNA Met mutation. The first patient, a 30-year-old woman, presented with exercise intolerance, limb girdle muscle weakness, lactic acidosis, learning difficulty, and growth retardation in early childhood. Thus, the two patients exhibit strikingly overlapping phenotypes. © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. 1. Introduction Mutations in mitochondrial encoded tRNA genes are among the most frequent causes of mitochondrial disease. Probable pathogenic mutations have been found in all 22 mitochondrial tRNAs, and they account for a large number of diverse clinical conditions, including MELAS (mitochondrial encephalomy- opathy, lactic acidosis, and stroke-like episodes), CPEO (chronic progressive external ophthalmoplegia), myoclonic epilepsy, encephalopathy, and cardiomyopathy. 1 So far, only a single pathogenic mutation giving rise to a mitochondrial myopathy has been described in the MT-TM gene encoding * Corresponding author. Paediatric Clinic, Paediatric Neurology 5003N, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen N, Denmark. Tel.: þ45 35455093; fax: þ45 35456717. E-mail address: peter.born@regionh.dk (A.P. Born). Official Journal of the European Paediatric Neurology Society european journal of paediatric neurology 19 (2015) 69 e71 http://dx.doi.org/10.1016/j.ejpn.2014.10.006 1090-3798/© 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.