RESUMEN
A 47-year-old man suffering from a bipolar disorder and intermittent myoglobinuria presented with acute rhabdomyolysis with renal failure after starting therapy with valproic acid. On morphological examination, skeletal muscle revealed increased lipid storage. Biochemically, decreased enzyme activity of carnitine palmitoyltransferase (CPT) type II with carnitine levels in the lower limit was found. Genetic analysis detected the common Ser113Leu substitution on one allele of the CPT2 gene. We conclude that valproic acid should be avoided in patients with CPT type II deficiency.
Asunto(s)
Antimaníacos/efectos adversos , Trastorno Bipolar/tratamiento farmacológico , Carnitina O-Palmitoiltransferasa/deficiencia , Rabdomiólisis/inducido químicamente , Rabdomiólisis/diagnóstico , Ácido Valproico/efectos adversos , Acetilcarnitina/análisis , Acetilcarnitina/metabolismo , Enfermedad Aguda , Trastorno Bipolar/complicaciones , Carnitina O-Palmitoiltransferasa/genética , Carnitina O-Palmitoiltransferasa/metabolismo , Humanos , Errores Innatos del Metabolismo Lipídico/complicaciones , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/enzimología , Masculino , Persona de Mediana Edad , Enfermedades Mitocondriales/complicaciones , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/enzimología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Mutación , Mioglobinuria/etiología , Rabdomiólisis/enzimologíaAsunto(s)
Carnitina O-Palmitoiltransferasa/deficiencia , Carnitina/sangre , Errores Innatos del Metabolismo/enzimología , Ésteres/sangre , Ácidos Grasos/sangre , Humanos , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Enfermedades Musculares/enzimología , Enfermedades Musculares/genética , Mioglobinuria/etiología , Mioglobinuria/genéticaRESUMEN
Multiple symmetric lipomatosis (MSL) is a rare disorder of middle life characterized by large nonencapsulated lipomas distributed around the neck, shoulders, and other axial regions. Neurologic involvement, particularly peripheral neuropathy, is frequent. The pathogenesis of the syndrome is still unknown, but ragged-red fibers are occasionally present in muscle of affected patients, suggesting a mitochondrial abnormality. We studied 11 unrelated patients with MSL by means of neurophysiology, muscle morphology, muscle biochemistry, Southern blot, and PCR analysis of mitochondrial DNA. All patients were men aged 41 to 63 years. Clinical or electrophysiologic signs of a sensorimotor polyneuropathy were present in nine patients, eight of whom had a history of alcoholism. In muscle biopsy specimens, the most prominent feature was pathologic subsarcolemmal aggregates of mitochondria. Biochemical analysis of respiratory chain enzymes revealed a moderate but significant decrease of cytochrome c oxidase activity as compared with age-matched controls. In one patient, Southern blot analysis showed multiple deletions of mitochondrial DNA. We conclude that mitochondrial dysfunction is common in MSL and may be based on identifiable defects in the mitochondrial genome.
Asunto(s)
Deleción Cromosómica , ADN Mitocondrial/genética , Lipomatosis/enzimología , Lipomatosis/genética , Adulto , Complejo IV de Transporte de Electrones/metabolismo , Humanos , Lipomatosis/patología , Masculino , Persona de Mediana Edad , Mitocondrias Musculares/enzimología , Mitocondrias Musculares/patología , Músculos/enzimología , Músculos/patologíaRESUMEN
Alterations of the mitochondrial DNA, encoding important parts of the cellular energy-generating system (oxidative phosphorylation, OXPHOS), are often associated with the occurrence of degenerative neuromuscular diseases. Especially point mutations in the mitochondrial tRNA genes, which cannot be complemented by the nuclear encoded tRNAs, are candidates for severe defects of the OXPHOS system. An A to G transition at nt 8344 in the tRNA(Lys) gene has been associated with MERRF disease whereas an A to G substitution at nt 3243 in the tRNA(Leu) gene has been linked to the MELAS syndrome. These two mtDNA alterations as well as point mutations in protein-coding genes can be detected simultaneously by an allele-specific amplification of the altered mtDNA. This assay allows the reliable detection of heteroplasmic point-mutations, even if the mutated DNA appears to a small extent of less than 1%.