1/8. MEHMO (Mental retardation, Epileptic seizures, Hypogenitalism, microcephaly, obesity): a new X-linked mitochondrial disorder.MEHMO (Mental retardation, Epileptic seizures, Hypogenitalism, microcephaly and obesity) is an X-linked disorder characterised by mental retardation, epileptic seizures, hypogenitalism, microcephaly and obesity. It was recently assigned to the locus Xp21.1-p22.13. We describe a child with MEHMO and lactic acidosis whose muscle biopsy revealed markedly reduced activities of complexes 1,3 and 4 of the mitochondrial electron transport chain. Histological staining showed mitochondrial proliferation and lipid storage. Electron microscopy revealed abnormal and enlarged mitochondria with concentric cristae and electron dense bodies. This is the first identification of MEHMO as a mitochondrial disorder and one of the very few X-linked mitochondrial syndromes.- - - - - - - - - - ranking = 1keywords = storage (Clic here for more details about this article) |
2/8. Defects of the mitochondrial respiratory chain complexes in three pediatric cases with hypotonia and cardiac involvement.Three children displaying hypotonia, cardiac involvement and defects of the mitochondrial respiratory chain complexes are reported. The first case showed severe neonatal hypotonia, failure to thrive, hepatomegaly, dilation of the right cardiac cavities, profound lactic acidosis and amino aciduria. The boy died at the age of 7 weeks. In the second case hypotonia, severe cardiomyopathy, cyclic neutropenia, lactic acidosis and 3-methylglutaconic aciduria occurred. The boy died at the age of 27 months. The third case presented at the age of 16 months as an acute hypokinetic hypertrophic cardiomyopathy with transient hypotonia and mild lactic acidosis. Spontaneous clinical remission occurred. In all cases muscle biopsy was performed. Morphological studies failed to show ragged-red fibers but there was lipid storage myopathy and decreased cytochrome c oxidase activity. Biochemical studies confirmed the cytochrome c oxidase deficiency in muscle in all cases. It was associated with complex I III deficiency in case 1 and with severe deficits of all respiratory chain complexes in case 2. Post-mortem studies in case 1 indicated that complex IV was reduced in the liver but not in the heart and quantitative analysis of mtDNA revealed a depletion in muscle. Cases 1 and 2 shared some clinical features with fatal infantile myopathy associated with cytochrome c oxidase deficiency, while case 3 displayed a very unusual clinical presentation. The histochemical enzyme reaction of cytochrome c oxidase is useful for the diagnosis of mitochondrial myopathy because ragged-red fibers may be lacking. Finally, biochemical measurement of the different mitochondrial respiratory chain complexes is required because multiple defects are frequent and occasionally related to mtDNA depletion.- - - - - - - - - - ranking = 1keywords = storage (Clic here for more details about this article) |
3/8. Hyperglycaemia associated with lactic acidaemia in a renal allograft recipient with type I glycogen storage disease.Renal disease is a frequent and serious complication of type I glycogen storage disease. A type I glycogen storage disease patient with focal segmental glomerulosclerosis and progressive renal insufficiency underwent a renal allograft transplantation. Despite the same cornstarch therapy, the post-transplantation course was complicated by worsening of the metabolic control manifested by exacerbated lactic acidaemia and hyperlipidaemia. This lactic acidaemia was remarkable for its association with hyperglycaemia. Hyperglycaemia accompanied by lactic acidaemia is strikingly unusual in type I glycogen storage disease, since this is a disease characterized by hypoglycaemia and an inverse relationship between blood glucose concentration and lactate levels. Both fasting insulin and c-peptide levels in the patient were greater than similar age-matched type I glycogen storage disease controls, indicating hyperinsulinaemia. The most likely mechanism responsible for the combined hyperglycaemia and lactic acidaemia was insulin resistance due to glucocorticoid treatment, instituted for immunosuppression. The hyperglycaemia associated with the lactic acidaemia was transient and resolved with steroid tapering. The exacerbated hyperlipidaemia, however, persisted after renal transplantation. Type I glycogen storage disease patients may be prone to glucocorticoid-induced insulin resistance, since the cellular metabolism in these patients may already be compromised with ineffective insulin action and/or reduced insulin output.- - - - - - - - - - ranking = 1608.1135197388keywords = glycogen storage disease, glycogen storage, storage disease, glycogen, storage (Clic here for more details about this article) |
4/8. Mitochondrial cytopathy with lactic acidosis, carnitine deficiency and DeToni-Fanconi-Debre syndrome.We reported a 6-year-old girl with mitochondrial cytopathy with lactic acidosis. The patient developed hypotonia, hearing loss, mental retardation, short stature, cataracta, hypoparathyroidism, DeToni-Fanconi-Debre syndrome and carnitine deficiency. Histological examination disclosed ragged red fibers and moderate lipid storage in skeletal muscle tissue and several structural abnormalities of mitochondria both in muscle tissue and proximal renal tubules. Biochemical examination of muscle tissue revealed a partial deficiency of pyruvate dehydrogenase complex and normal activities of cytochrome c oxidase, succinate cytochrome c reductase and NADH cytochrome c reductase. This is the first report of mitochondrial cytopathy representing DeToni-Fanconi-Debre syndrome associated with partial deficiency of pyruvate dehydrogenase complex and normal cytochrome c oxidase activity.- - - - - - - - - - ranking = 1keywords = storage (Clic here for more details about this article) |
5/8. Bilateral infantile cataractogenesis in a patient with deficiency of complex I, a mitochondrial electron transport chain enzyme.Progressive bilateral cataracts developed in infancy in a 5-month-old girl with deficiency of complex I, a mitochondrial electron transport chain enzyme. In the newborn period, she had severe lactic acidosis and the diagnosis of complex I deficiency was confirmed by mitochondrial respiratory chain assay on muscle biopsy. By 5 months, she had completely opaque nuclear sclerotic cataracts, with loss of fixation and the red reflex. She underwent bilateral, sequential cataract extraction. The lens aspirate was submitted for cytologic analysis and electron microscopy, which revealed increased intracellular glycogen and swollen mitochondria. To our knowledge the association of complex I deficiency with cataracts in infancy has not been reported previously. The diagnosis of a respiratory chain enzyme defect in infancy is an indication for early ophthalmic evaluation to identify cataracts that may result in visual loss. Conversely, the recognition of cataracts in infants with unexplained neurologic disease or metabolic acidosis may necessitate further evaluation for metabolic etiologies, including mitochondrial disorders.- - - - - - - - - - ranking = 5.4262902939992keywords = glycogen (Clic here for more details about this article) |
6/8. oxidative phosphorylation defect associated with primary adrenal insufficiency.An 18-month-old girl with an oxidative phosphorylation defect had neonatal onset of chronic lactic acidosis, lipid storage myopathy, bilateral cataracts, and primary adrenal insufficiency. Chronic lactic acidosis responded to treatment with dichloroacetate. Sequential muscle biopsies demonstrated resolution of the lipid storage myopathy associated with the return to normal muscle free carnitine levels. This case demonstrates a new clinical phenotype associated with a defect in oxidative phosphorylation and the need to consider mitochondrial disorders in the differential diagnosis of primary adrenal insufficiency in childhood.- - - - - - - - - - ranking = 2keywords = storage (Clic here for more details about this article) |
7/8. Mitochondrial electron transport chain defect presenting as hypoglycemia.A profoundly deaf female infant was found to have hypoglycemia and lactic acidemia after an episode of decreased oral intake and vomiting. electron transport chain (ETC) enzyme studies revealed a combination defect of complexes I, III, and IV in liver but not in skeletal muscle. This case highlights the fact that defects of the ETC are clinically highly heterogeneous and should be considered with hypoglycemia and lactic acidosis in the absence of a glycogen storage disorder. Moreover, ETC defects can occur with a biochemical profile suggestive of a fatty acid oxidation disorder.- - - - - - - - - - ranking = 66.745361205956keywords = glycogen storage, glycogen, storage (Clic here for more details about this article) |
8/8. Treatment with low-dose diazoxide in two growth-retarded prepubertal girls with glycogen storage disease type Ia resulted in catch-up growth.Two originally prepubertal girls suffering from glycogen storage disease type Ia and short stature were treated with low-dose diazoxide (3-4.8 mg/kg per day) for 7 and 4 years, respectively. Both showed an impressive catch-up growth following this treatment. This appeared to be due to prolongation of normoglycaemia after meals and reduction of fasting lactic acidosis by diazoxide.- - - - - - - - - - ranking = 963.35509908301keywords = glycogen storage disease, glycogen storage, storage disease, glycogen, storage (Clic here for more details about this article) |