RESUMEN
COQ4 mutations have recently been shown to cause a broad spectrum of mitochondrial disorders in association with CoQ10 deficiency. Herein, we report the clinical phenotype, in silico and biochemical analyses, and intervention for a novel c.370 G > A (p.G124S) COQ4 mutation in a Chinese family. This mutation is exclusively present in the East Asian population (allele frequency of ~0.001). The homozygous mutation caused CoQ10 deficiency-associated Leigh syndrome with an onset at 1-2 months of age, presenting as respiratory distress, lactic acidosis, dystonia, seizures, failure to thrive, and detectable lesions in the midbrain and basal ganglia. No renal impairment was involved. The levels of CoQ10 and mitochondrial respiratory chain complex (C) II + III activity were clearly lower in cultured fibroblasts derived from the patient than in those from unaffected carriers; the decreased CII + III activity could be increased by CoQ10 treatment. Follow-up studies suggested that our patient benefitted from the oral supplementation of CoQ10, which allowed her to maintain a relatively stable health status. Based on the genetic testing, preimplantation and prenatal diagnoses were performed, confirming that the next offspring of this family was unaffected. Our cases expand the phenotypic spectrum of COQ4 mutations and the genotypic spectrum of Leigh syndrome.
Asunto(s)
Ataxia/genética , Pruebas Genéticas , Enfermedad de Leigh/genética , Enfermedades Mitocondriales/genética , Proteínas Mitocondriales/genética , Debilidad Muscular/genética , Ubiquinona/deficiencia , Pueblo Asiatico/genética , Ataxia/complicaciones , Preescolar , Simulación por Computador , Femenino , Fibroblastos/metabolismo , Heterocigoto , Homocigoto , Humanos , Lactante , Enfermedad de Leigh/complicaciones , Enfermedad de Leigh/fisiopatología , Masculino , Mitocondrias/genética , Mitocondrias/patología , Enfermedades Mitocondriales/complicaciones , Debilidad Muscular/complicaciones , Mutación , Fenotipo , Ubiquinona/genética , Ubiquinona/farmacocinéticaRESUMEN
The case is presented of a 3 year-old girl with mitochondrial disease (subacute necrotizing encephalomyelopathy of Leigh syndrome), v-stage chronic kidney disease of a diffuse mesangial sclerosis, as well as developmental disorders, and diagnosed with hyperthyroidism Graves-Basedow disease. Six weeks after starting the treatment with neo-carbimazole, the patient reported a serious case of agranulocytosis. This led to stopping the anti-thyroid drugs, and was treated successfully with 131I ablation therapy. The relevance of the article is that Graves' disease is uncommon in the paediatric age range (especially in children younger than 6 years old), and developing complications due to a possible late diagnosis. Agranulocytosis as a potentially serious adverse effect following the use of anti-thyroid drugs, and the few reported cases of ablation therapy with 131I at this age, makes this case unique.
Asunto(s)
Agranulocitosis/inducido químicamente , Antitiroideos/efectos adversos , Carbimazol/efectos adversos , Enfermedad de Graves/radioterapia , Radioisótopos de Yodo/uso terapéutico , Agranulocitosis/terapia , Antitiroideos/uso terapéutico , Transfusión Sanguínea , Carbimazol/uso terapéutico , Preescolar , Discapacidades del Desarrollo/complicaciones , Quimioterapia Combinada , Femenino , Enfermedad de Graves/complicaciones , Enfermedad de Graves/tratamiento farmacológico , Humanos , Enfermedad de Leigh/complicaciones , Síndrome Nefrótico/complicaciones , Propranolol/uso terapéutico , Esclerosis/complicacionesRESUMEN
Leigh syndrome is a mitochondrial disease characterized by subacute necrotizing encephalomyelopathy. Almost all cases of Leigh syndrome develop at infancy or early childhood and die within several years due to rapidly progressive muscle weakness and respiratory failure. Here, we present a rare case of a patient who developed Leigh syndrome associated with thiamine-responsive pyruvate dehydrogenase-complex deficiency at 2 years of age and has survived to adolescence through effective high dose thiamin therapy. At 15 years of age, the patient presented persecutory delusions and auditory hallucinations, suggesting an association between mitochondrial dysfunction and schizophrenia-like psychotic symptoms.
Asunto(s)
Enfermedad de Leigh/complicaciones , Trastornos Psicóticos/etiología , Adolescente , Humanos , Masculino , Esquizofrenia/etiologíaAsunto(s)
Creatina/uso terapéutico , Enfermedad de Leigh/terapia , Ataxia/etiología , Ataxia/terapia , Preescolar , Creatina/administración & dosificación , Suplementos Dietéticos , Femenino , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Humanos , Enfermedad de Leigh/complicaciones , Enfermedad de Leigh/patología , Imagen por Resonancia Magnética , Trastornos Respiratorios/etiología , Trastornos Respiratorios/terapiaRESUMEN
We report on a boy who developed proximal renal tubular acidosis with loss of carnitine at the age of about 6 months. A few months later he began to suffer from progressive muscular weakness and neurological disturbances. Blood biochemistry showed elevated lactate and beta-hydroxybutyrate with increased lactate/pyruvate and beta-hydroxybutyrate/acetoacetate ratios. A high urinary excretion of lactate and citric acid cycle intermediates was found. These results indicated a defect of the mitochondrial respiratory chain. Analysis of biopsy material from skeletal muscle revealed low activities of all respiratory chain complexes. In muscle and fibroblasts cytochrome c-oxidase (complex IV) was absent. Despite high dose multi-vitamin therapy the boy died at the age of 30 months from central respiratory failure. At autopsy the neuropathological diagnosis of Leigh disease was made.