Exercise intolerance, muscle pain and lactic acidaemia associated with a 7497G>A mutation in the tRNASer(UCN) gene

• Published in: Journal of inherited metabolic disease 2003, Vol.26 (6), p.593-600
• Main Authors: Grafakou, O., Hol, F. A., Otfried Schwab, K., Siers, M. H., Ter Laak, H., Trijbels, F., Ensenauer, R., Boelen, C., Smeitink, J.
• Format: Article
• Language: English
• Subjects: Acidosis, Lactic - complications; Acidosis, Lactic - genetics; Adolescent; Biological and medical sciences; Brain - pathology; DNA, Mitochondrial - genetics; Electrocardiography; Electroencephalography; Electromyography; Evoked Potentials, Auditory - physiology; Evoked Potentials, Somatosensory - physiology; Exercise Tolerance - genetics; Feeding. Feeding behavior; Female; Fibroblasts - enzymology; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Humans; Magnetic Resonance Imaging; Molecular and cellular biology; Muscle, Skeletal - enzymology; Muscle, Skeletal - pathology; Muscular Diseases - genetics; Muscular Diseases - pathology; Oxidation-Reduction; Pain - complications; Pain - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Transfer, Ser - genetics; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1023/A:1025960300710

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.