A mitochondrial tRNA(Met) mutation causing developmental delay, exercise intolerance and limb girdle phenotype with onset in early childhood

TY - JOUR

T1 - A mitochondrial tRNA(Met) mutation causing developmental delay, exercise intolerance and limb girdle phenotype with onset in early childhood

AU - Born, Alfred Peter

AU - Duno, Morten

AU - Rafiq, Jabin

AU - Risom, Lotte

AU - Wibrand, Flemming

AU - Østergaard, Elsebet

AU - Vissing, John

N1 - Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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 mitochondrial 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 myopathy 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.

AB - 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 mitochondrial 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 myopathy 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.

KW - Acidosis, Lactic

KW - Age of Onset

KW - Child

KW - DNA, Mitochondrial

KW - Developmental Disabilities

KW - Exercise Tolerance

KW - Extremities

KW - Female

KW - Growth Disorders

KW - Humans

KW - Learning Disorders

KW - Magnetic Resonance Imaging

KW - Mitochondrial Diseases

KW - Muscle Fibers, Skeletal

KW - Muscle Weakness

KW - Mutation

KW - Neurologic Examination

KW - RNA, Transfer, Met

U2 - 10.1016/j.ejpn.2014.10.006

DO - 10.1016/j.ejpn.2014.10.006

M3 - Journal article

C2 - 25468263

SN - 1090-3798

VL - 19

SP - 69

EP - 71

JO - European Journal of Paediatric Neurology

JF - European Journal of Paediatric Neurology

IS - 1

ER -