RESUMEN
Mitochondria are best known for their role in energy production, and they are the only mammalian organelles that contain their own genomes. The mitochondrial genome mutation rate is reported to be 10-17 times higher compared to nuclear genomes as a result of oxidative damage caused by reactive oxygen species during oxidative phosphorylation. Pathogenic mitochondrial DNA mutations result in mitochondrial DNA disorders, which are among the most common inherited human diseases. Interventions of mitochondrial DNA disorders involve either the transfer of viable isolated mitochondria to recipient cells or genetically modifying the mitochondrial genome to improve therapeutic outcome. This review outlines the common mitochondrial DNA disorders and the key advances in the past decade necessary to improve the current knowledge on mitochondrial disease intervention. Although it is now 31 years since the first description of patients with pathogenic mitochondrial DNA was reported, the treatment for mitochondrial disease is often inadequate and mostly palliative. Advancements in diagnostic technology improved the molecular diagnosis of previously unresolved cases, and they provide new insight into the pathogenesis and genetic changes in mitochondrial DNA diseases.
Asunto(s)
ADN Mitocondrial/genética , Edición Génica/métodos , Terapia Genética/métodos , Mitocondrias/genética , Enfermedades Mitocondriales/genética , Acidosis Láctica/congénito , Acidosis Láctica/genética , Acidosis Láctica/metabolismo , Análisis Mutacional de ADN , ADN Mitocondrial/metabolismo , Epilepsias Mioclónicas/congénito , Epilepsias Mioclónicas/genética , Epilepsias Mioclónicas/terapia , Humanos , Enfermedad de Leigh/genética , Enfermedad de Leigh/metabolismo , Enfermedad de Leigh/terapia , Mitocondrias/metabolismo , Mitocondrias/patología , Enfermedades Mitocondriales/metabolismo , Enfermedades Mitocondriales/terapia , Encefalomiopatías Mitocondriales/congénito , Encefalomiopatías Mitocondriales/genética , Encefalomiopatías Mitocondriales/metabolismo , Mutación , Atrofia Óptica Hereditaria de Leber/genética , Atrofia Óptica Hereditaria de Leber/metabolismoRESUMEN
Norrie disease (ND) is an X-linked disorder, inherited as a recessive trait that, therefore, mostly affects males. The gene responsible for ND, called NDP, maps to the short arm of chromosome X (Xp11.4-p11.3). We report here an atypical case of ND, consisting of a patient harboring a large submicroscopic deletion affecting not only the NDP gene but also the MAOA, MAOB, and EFHC2 genes. Microarray comparative genomic hybridization (CGH) analysis showed that 11 consecutive bacterial artificial chromosome (BAC) clones, mapping around the NDP gene, were deleted. These clones span a region of about 1 Mb on Xp11.3. The deletion was ascertained by fluorescent in situ hybridization (FISH) analysis with different BAC clones located within the region. Clinical features of the proband include bilateral retinal detachment, microcephaly, severe psychomotor retardation without verbal language skills acquired, and epilepsy. The identification and molecular characterization of this case reinforces the idea of a new contiguous gene syndrome that would explain the complex phenotype shared by atypical ND patients.
Asunto(s)
Ceguera/congénito , Proteínas de Unión al Calcio/genética , Epilepsias Mioclónicas/genética , Proteínas del Ojo/genética , Monoaminooxidasa/genética , Proteínas del Tejido Nervioso/genética , Trastornos Psicomotores/genética , Ceguera/genética , Niño , Deleción Cromosómica , Cromosomas Humanos X , Epilepsias Mioclónicas/congénito , Humanos , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Trastornos Psicomotores/congénitoRESUMEN
We report on a male infant with pyridoxine dependency and seizures from birth, controlled with pharmacological doses of pyridoxine at 4 months of age. Seizures stopped between 30 and 80 days of age when very-low doses of pyridoxine were given in a multivitamin supplement. Daily dose was 0.5 mg that corresponded to 0.08 to 0.16 mg/kg/day when weight gain is considered. In previous reports doses have ranged from 0.2 to 30 mg/kg/day. Another distinctive feature was that this infant went into a coma and developed hypotonia and irregular breathing when pyridoxine was given by enteral tube which has usually been reported when the vitamin is given intravenously. Use of low doses of pyridoxine in multivitamin supplements could be a confounding factor for early diagnosis and appropriate treatment of pyridoxine-dependent seizures.
Asunto(s)
Coma/inducido químicamente , Discapacidades del Desarrollo/etiología , Epilepsias Mioclónicas/congénito , Errores Innatos del Metabolismo/complicaciones , Errores Innatos del Metabolismo/tratamiento farmacológico , Hipotonía Muscular/inducido químicamente , Piridoxina/administración & dosificación , Piridoxina/metabolismo , Trastornos Respiratorios/inducido químicamente , Factores de Edad , Peso Corporal , Factores de Confusión Epidemiológicos , Monitoreo de Drogas , Electroencefalografía , Nutrición Enteral , Epilepsias Mioclónicas/diagnóstico , Genes Recesivos , Humanos , Lactante , Masculino , Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/genética , Piridoxina/efectos adversosRESUMEN
BACKGROUND: Neonatal myoclonic encephalopathy is of lesional or metabolic origin; non ketotic hyperglycinemia is one of its causes. CASE REPORT: A girl, born from consanguineous parents, died from myoclonic epileptic encephalopathy at the age of 3 months. Screening for metabolic disease was negative, except for increased levels of urine serotonin and 5-hydroxyindol-acetic in cerebrospinal fluid, blood and urine. Two sisters died with non ketotic hyperglycinemia, corpus callosum agenesis and clubfoot. CONCLUSION: Familial occurrence of non ketotic hyperglycinemia and early myoclonic epileptic encephalopathy is uncommon.