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Oxidative stress may be implied in the pathogenic mechanisms of inborn errors of intermediary metabolism (IEIM).The evaluation of the antioxidant status in IEIM by the measurement of erythrocyte antioxidant enzyme activities, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase and catalase.34 patients with IEIM: 1) eleven with organic acidurias on protein restricted diet; 2) nine without special diet; 3) five patients with aminoacidopathies on protein restriction; 4) three patients with galactosemia and six with aminoacidopathies on protein free diet. Erythrocyte antioxidant enzymes were measured by spectrometric procedures adapted to the Cobas Fara II analyser.SOD activity was significantly higher in groups 2 and 4 (p= 0.009, p= 0.001, respectively), and significantly lower in group 3 (p= 0.001) compared with age matched controls. SOD activity was significantly higher in the patients with IEIM on protein free diet (groups 2 and 4) compared with those on protein restricted diet (groups 1 and 3; p= 0.002) or with controls (p= 0.003). GPx activity was found significantly lower in group 1 patients (p= 0.004), and higher in group 2 (p= 0.029) compared with controls.35% of the patients with IEIM had SOD activity above the control range, most of them with organic acidurias or homocystinuria, suggesting an induction of enzyme protein synthesis owing to an excess of free radical generation. The lower activities observed in patients on natural protein restriction may likely be due to a deficient bioavailability of antioxidant cofactors.

Introduction. Carnitine is an nonproteic nitrogenated compound acid present in all mammalian tissue and its principal activity is the long-chain fatty acid transport across the mitochondrial membrane for beta-oxidation. Development. Carnitine levels ale maintained by absorption from dietary, endogenous synthesis in the liver and venal reabsorption. An alteration in concentration could be due to an abnormality in some of mentioned mechanism or to inherited errors in metabolism. A reduction in serum carnitine levels have been reported in patients with antiepileptic drugs (AED) use. While valproic acid as monotheraphy or in combination with other AED have been associated principally, some contradictory studies demonstrated that other AED specifically carbamazepine, phenytoin and phenobarbital, also cause carnitine deficiency in about 21% of the patients whom they are administered Conclusion. This study was designed to investigated the relationship between the carnitine levels and the presence of symptoms in patients with seizures whom ave treated with a AED alone or in combination.

Introduction. The existence of neuropathy has been described in mitochondrial disorders such as MELAS, MERRF, Leigh's syndrome, the Kearns-Saye syndrome, myoneurogastro-intestinal encephalopathy and progressive external ophthalmoplegia and constitutes a basic component of the NARP (neuropathy, ataxia and retinosis pigmentosa). However, the general prevalence of the neuropathy and its characteristics within the mitochondrial encephalopathies is not well understood. Objectives. To characterize the neuropathy and try to establish a genotype-phenotype correlation. Patients and methods. within study guidelines, we made a retrospective study of 27 patients, diagnosed as having mitochondrial disease, who had had neurophysiological studies (EMG-ENG). In those in whom neuropathy had been found we analysed the clinical, neurophysiological and genetic characteristics. Results. Neuropathy was present in 37% of the patients who had an average age of 13 years, ranging from I to 25 years. Syndromic diagnoses were: 7 encephalomyopathies, one MELAS, one MERRF and one NARP. Four of the patients were classified genetically. In all but two of the patients the neuropathy was asymptomatic. The biochemical alterations seen were: deficit of Complex 1 in 3 patients, of complex III in 3 patients, of complex IV in 2 and of pyruvate dehydrogenase in one patient. The type of neuropathy found was varied with predominance of axonal-type motor neuropathy but no correlation with either biochemical defects or genetic diagnosis. Conclusions. Neuropathy is a common finding in mitochondrial disorders and probably is under-diagnosed. The axonal form predominates. We hats not been able to establish correlations between phenotypes and genotypes.

Review of ubiquinone-10 metabolism and functions in humans, focusing its implication in the pathogenesis and physiopathology of mitochondrial encephalomyopathies.

INTRODUCTION: The correct selection of pediatric patients with clinical suspicion of mitochondrial diseases is the first step to achieve a definitive diagnosis. MATERIAL AND METHODS: The results of the initial biochemical tests obtained in 35 children diagnosed of respiratory chain or pyruvate metabolism defects were reviewed. The efficiency of basal determinations (lactate, pyruvate, ketone bodies, amino and organic acids and carnitine), cerebrospinal fluid (CSF) analysis, and dynamic tests (exercise, glucose loading and glucose oxidation by lymphocytes) was discussed. RESULTS: Plasma lactate and alanine, and CSF metabolites were the most informative measurements in basal status. Urine organic acids were very useful to confirm the initial suspicion. Glucose loading was the most informative and reliable challenge test for pediatric population, while exercise test was especially useful for older children with fatigability or peripheral nervous system involvement. CONCLUSIONS: Glucose oxidation by lymphocytes might be applied when the other dynamic tests can not be performed or are not informative.