TY - JOUR
T1 - Recurrent myoglobinuria in a sporadic patient with a novel mitochondrial DNA tRNAIle mutation
AU - Emmanuele, Valentina
AU - Sotiriou, Evangelia
AU - Shirazi, Maryam
AU - Tanji, Kurenai
AU - Haller, Ronald G.
AU - Heinicke, Katja
AU - Bosch, Peter E.
AU - Hirano, Michio
AU - Dimauro, Salvatore
N1 - Funding Information:
Part of the work described here is supported by NIH grant HD32062 and by the Marriott Mitochondrial Disorder Clinical Research Fund (MMDCRF) .
PY - 2011/4/15
Y1 - 2011/4/15
N2 - The differential diagnosis of myoglobinuria includes multiple etiologies, such as infection, inflammation, trauma, endocrinopathies, drugs toxicity, and primary metabolic disorders. Metabolic myopathies can be due to inherited disorders of glycogen metabolism or to defects of fatty acid oxidation. Primary respiratory chain dysfunction is a rare cause of myoglobinuria, but it has been described in sporadic cases with mutations in genes encoding cytochrome b or cytochrome c oxidase (COX) subunits and in four cases with tRNA mutations. We describe a 39-year-old woman with myalgia and exercise-related recurrent myoglobinuria, who harbored a novel mitochondrial DNA mutation at nucleotide 4281 (m.4281A>G) in the tRNA-isoleucine gene. Her muscle biopsy revealed ragged-red and COX-deficient fibers. No deletions or duplication were detected by Southern blot analysis. The m.4281A>G mutation was present in the patient's muscle with a mutation load of 46% and was detected in trace amounts in urine and cheek mucosa. Single-fiber analysis revealed significantly higher levels of the mutation in COX-deficient (65%) than in normal fibers (45%). This novel mutation has to be added to the molecular causes of recurrent myoglobinuria.
AB - The differential diagnosis of myoglobinuria includes multiple etiologies, such as infection, inflammation, trauma, endocrinopathies, drugs toxicity, and primary metabolic disorders. Metabolic myopathies can be due to inherited disorders of glycogen metabolism or to defects of fatty acid oxidation. Primary respiratory chain dysfunction is a rare cause of myoglobinuria, but it has been described in sporadic cases with mutations in genes encoding cytochrome b or cytochrome c oxidase (COX) subunits and in four cases with tRNA mutations. We describe a 39-year-old woman with myalgia and exercise-related recurrent myoglobinuria, who harbored a novel mitochondrial DNA mutation at nucleotide 4281 (m.4281A>G) in the tRNA-isoleucine gene. Her muscle biopsy revealed ragged-red and COX-deficient fibers. No deletions or duplication were detected by Southern blot analysis. The m.4281A>G mutation was present in the patient's muscle with a mutation load of 46% and was detected in trace amounts in urine and cheek mucosa. Single-fiber analysis revealed significantly higher levels of the mutation in COX-deficient (65%) than in normal fibers (45%). This novel mutation has to be added to the molecular causes of recurrent myoglobinuria.
KW - Elevated serum CK
KW - Mitochondrial DNA
KW - Mitochondrial myopathy
KW - Myalgia
KW - Myoglobinuria
KW - tRNA
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U2 - 10.1016/j.jns.2011.01.018
DO - 10.1016/j.jns.2011.01.018
M3 - Article
C2 - 21324494
AN - SCOPUS:79952818365
SN - 0022-510X
VL - 303
SP - 39
EP - 42
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
IS - 1-2
ER -