Exercise intolerance, muscle pain and lactic acidaemia associated with a 7497G>A mutation in the tRNASer(UCN) gene.
A 13-year-old girl with non-familial exercise intolerance, muscle pain and lactic acidaemia underwent a muscle biopsy for suspected mitochondrial disease. Muscle morphology showed 25% ragged-red fibres and 80% COX-negative staining. Enzymatic activities of mitochondrially co-encoded respiratory chain enzymes (complexes I, III, and IV) were decreased in muscle but normal in cultured skin fibroblasts. mtDNA analysis revealed the presence of the 7497G>A mutation in the tRNASer(UCN) gene, homoplasmic in skeletal muscle and 90% in leukocytes. Analysis of the mother's mtDNA showed 10% heteroplasmy in blood. It may be concluded that the 7497G>A mutation is associated with a muscle-only disease presentation for which high levels of mutated mtDNA are required. Exercise intolerance and muscle pain in otherwise normal children warrants further mitochondrial evaluation.
Grafakou
O
O
Department of Pediatrics, Nijmegen Center for Mitochondrial Disorders, University Medical Center Nijmegen, The Netherlands.
Hol
F A
FA
Otfried Schwab
K
K
Siers
M H
MH
ter Laak
H
H
Trijbels
F
F
Ensenauer
R
R
Boelen
C
C
Smeitink
J
J
D000140:Acidosis, Lactic / Q000150:complications / Q000235:genetics*; D000293:Adolescent; D001921:Brain / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics; D004562:Electrocardiography; D004569:Electroencephalography; D004576:Electromyography; D005072:Evoked Potentials, Auditory / Q000502:physiology; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D017079:Exercise Tolerance / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D008279:Magnetic Resonance Imaging; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology; D010084:Oxidation-Reduction; D010146:Pain / Q000150:complications / Q000235:genetics*; D012362:RNA, Transfer, Ser / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004272:DNA, Mitochondrial; D012362:RNA, Transfer, Ser