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Biomedical subjects

M Castro-Gago

Publications and source records attributed to M Castro-Gago.

At least 55 records · Page 3Linked to original sources
PubMed1996

Leber's congenital amaurosis associated with mitochondrial dysfunction.

We report the case histories of two 6-month-old girls, both with young, nonconsanguineous parents, referred to us for suspected blindness. In both cases, Leber's congenital amaurosis was diagnosed. Due to persistently high lactic acid levels in blood, muscle biopsies were taken. Analysis of biopsies revealed that both patients had low levels of complex IV of the mitochondrial respiratory chain; one patient additionally had low levels of complex III. Microscopic and ultrastructural alterations of muscle, typically observed in mitochondrial disorders, were observed only in the second patient. These observations raise the possibility that at least some cases of Leber's congenital amaurosis may be due to alterations in the mitochondrial respiratory chain.

Age of Onset↗
PubMed1996

[Pyruvate dehydrogenase deficiency and cerebral malformations].

Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and severe global developmental delay. A deficiency of PDH E1 alpha, a subunit of the PDH complex is a prominent cause of congenital lactic acidosis. The E1 alpha cDNA and corresponding genomic DNA have been located in the short arm of the X-chromosome (Xp22-1). A isolated 'cerebral' lactic acidosis with cerebral dysgenesis is a recognized pattern of presentation of PDH deficiency. Here, we report clinical features, magnetic resonance, and biochemical studies of two females aged 6 months (case 1) and 26 months (case 2). Both had severe development delay, minor dysmorphic features, microcephaly, severe hypoplasia of the corpus callosum, cerebral atrophy, ventricular dilatation and increase in serum lactate levels without systemic acidosis. Urinary organic acid profile was compatible with PDH deficiency. Increased CSF lactate and pyruvate levels and reduced total PDH and PDH E1 activities in muscle and fibroblasts were observed in case 1. Otherwise, decreased total PDH activity in muscle but not in fibroblasts was seen in case 2. The PDH E1á gene was sequenced in the case 1 and a deletion in exon 7 was demonstrated. Dysmorphism with severe cerebral malformations in female patients merits a metabolic evaluation, including determination of lactate and pyruvate levels in CSF.

Brain↗
PubMed1995

Purine and carnitine metabolism in muscle of patients with Duchenne muscular dystrophy.

We determined levels of purines, purine metabolites, related enzymes and carnitine in muscle of 8 untreated Duchenne muscular dystrophy (DMD) patients, 12 allopurinol-treated DMD patients and 12 age-matched controls. Muscle of DMD patients was found to be deficient in ATP, ADP, adenylsuccinate, hypoxanthine, guanine and adenylsuccinate synthetase. In allopurinol-treated DMD patients, mean total adenylate level was only three times less than in controls (versus 14 times less in untreated DMD patients). Mean inosine monophosphate (IMP), adenine, adenosine, inosine, xanthine, guanine, guanosine and uric acid levels were higher in allopurinol-treated patients than in controls, while mean adenylsuccinate levels were higher than in untreated patients. Allopurinol also restored acylcarnitine levels to normal and significantly increased free carnitine levels. These findings strongly support the hypothesis that Duchenne muscular dystrophy involves alterations leading to blockage of the IMP-->purine pathway and that allopurinol treatment favours restoration of purine levels by this route. Furthermore, our results suggest that the observed deficiencies in cell components unrelated to purine metabolism are long-term secondary effects.

Adolescent↗
PubMed1995

Severe myoclonic epilepsy associated with mitochondrial cytopathy.

We describe a case in which severe myoclonic epilepsy of infancy is associated with a disturbance in mitochondrial function. EEG traces showed diffuse spike-wave patterns inducible by intermittent photic stimulation. Laboratory analyses revealed high lactic acid levels in cerebrospinal fluid and urine, without metabolic acidosis or high lacticacidaemia. Muscle biopsy showed a slight increase in the number of mitochondria, which had a tendency towards subsarcolemmal locations, and clefts in the myofibrillar membrane that contained granular material staining positive for oxidative enzymes and red with modified Gomori stain. Quantification of the enzymatic activities of homogenized muscle showed partial deficiency of the mitochondrial respiratory chain complexes III and IV. Severe myoclonic epilepsy associated with mitochondrial cytopathy was diagnosed, but the possibility cannot be ruled out that the myoclonic epilepsy (or perhaps simply nonspecific epileptic encephalopathy) was secondary to the mitochondrial cytopathy. Thorough diagnostic analysis in severe myoclonic epilepsy cases is called for with a view to elucidation of a possible metabolic aetiology.

Biopsy↗
PubMed1995

Cerebrospinal fluid purine metabolites and pyrimidine bases after brief febrile convulsions.

Adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid, and pyrimidines bases were determined in cerebrospinal fluid (CSF) of 52 children after simple febrile seizures and in a control group of 63 children. There was no statistically significant difference between the two groups for any of these metabolites, suggesting that simple febrile seizures (SFS) neither significantly disturb the metabolism of nucleotides, nucleosides, or bases nor significantly deplete neuron adenosine ATP levels. Therefore, they do not appear to constitute a threat of neuronal damage.

Child, Preschool↗
PubMed1995

Effects of long-term treatment with antiepileptic drugs on serum lipid levels in children with epilepsy.

We determined serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TGs) in 125 healthy children and in 119 children with epilepsy who had been receiving carbamazepine (58 children), phenobarbital (22 children), or valproic acid (39 children) for 7 months to 10.5 years (mean, 5.8 years). None of the variables considered was significantly correlated with time elapsed since start of treatment or with drug concentration in serum. In the groups receiving carbamazepine or phenobarbital, mean TC, HDL-C, and LDL-C levels were higher than in the control group, the differences being statistically significant for all except LDL-C in the phenobarbital group. In neither group did mean TC/HDL-C ratio or mean LDL-C/HDL-C ratio differ significantly from the corresponding control-group mean. In the group receiving valproic acid, mean TC level, mean LDL-C level, mean TC/HDL-C ratio, and mean LDL-C/HDL-C ratio were significantly lower than in the control group. In none of the treated groups did mean VLDL-C or TG level differ significantly from the corresponding control-group mean. Our results suggest, in contrast to previous reports, that the effects on the serum lipid profile of long-term treatment with hepatic-enzyme-inducing antiepileptic drugs (such as carbamazepine and phenobarbital) are probably not beneficial as regards risk of atherosclerosis-related disease. Our results additionally suggest a need for careful monitoring of serum cholesterol levels in children with epilepsy receiving carbamazepine or phenobarbital.

Anticonvulsants↗
PubMed1993

Indicators of hypoxia in cerebrospinal fluid of hydrocephalic children with suspected shunt malfunction.

We used high performance liquid chromatography to determine the concentration of purine metabolites in the cerebrospinal fluid of three hydrocephalic children with a history of shunt malfunction. Hypoxanthine and xanthine levels were high in comparison with controls. We consider these purines to be valuable indicators of disturbance of neuronal metabolism following the sustained rise in intracranial pressure caused by shunt valve malfunction.

Adolescent↗
PubMed1993

Concentrations of nucleotides, nucleosides, purine bases and urate in cerebrospinal fluid of children with meningitis.

The release of agents mediating inflammation in meningitis may bring about neuronal hypoxia, under which circumstances ATP concentrations decrease and its degradation products increase and are released into the cerebrospinal fluid. In this study of alterations in neuronal energy metabolism in meningitis, AMP, IMP, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine and urate were determined by high performance liquid chromatography in the cerebrospinal fluid of 54 children aged between 1 month and 13 years suffering from meningitis (25 viral, 24 bacterial and 5 tuberculous cases) and 63 controls. Compared to the controls, patients with viral meningitis exhibited high concentrations of IMP, adenosine, guanosine, adenine, guanine and xanthine; patients with bacterial meningitis exhibited high concentrations of IMP, inosine, guanosine, adenosine, hypoxanthine, xanthine and urate; and patients with tuberculous meningitis exhibited high concentrations of AMP, guanosine, xanthine and urate. Viral and bacterial cases did not differ significantly for any of the metabolites studied. AMP and urate concentrations were significantly higher in patients with tuberculous cases compared with viral or bacterial meningitis cases.

Adenosine Monophosphate↗
PubMed1993

[Familial agenesis of the corpus callosum: a new form].

BACKGROUND. Agenesis of the corpus callosum is generally associated with other developmental defects of the cerebrum. Some familial cases have been reported. CASES REPORTS Case n. 1. A 6 year-old girl was examined because of developmental retardation, first noted at the age of 3 months. There was no consanguinity but 2 girls, cousins of the father, died at 17 and 18 years with the same clinical presentation. Our patient had seizures at 4 years. At examination, she had microcephaly, dilated unreactive pupils, and generalized hypotonia. Her IQ was 15. Funduscopic examination showed optic atrophy and visual evoked potentials were abnormal. The EEG showed spike-wave discharges and the CT scan showed agenesis of the corpus callosum plus heterotopias of the grey matter and brain atrophy. The child died at 12 years of age. Case n. 2. At 15 month-old girl, sister of case n. 1, had shown developmental retardation since the age of 4 months. She had microcephaly, dilated unreactive pupils, generalized hypotonia. Her IQ was 20. She also had optic atrophy, abnormal visual evoked potentials and a hypsarrhythmic pattern on EEG. The CT scan showed agenesis of corpus callosum plus heterotopias of the grey matter and brain atrophy. She died at the age of 10 years. Case n. 3. This boy, brother of cases 1 and 2, was examined on the first day of life. He had microcephaly and some spike-wave discharges on EEG. The CT scan and MRI showed agenesis of the corpus callosum. He had generalized hypotonia at 5 months with an IQ of 30; he suffered from seizures at 18 months. CONCLUSIONS. This agenesis of the corpus callosum seems to have an autosomal recessive inheritance. The associated developmental defects are different from those previously reported, suggesting that these cases represent a new form of corpus callosum lack.

Abnormalities, Multiple↗
PubMed1992

Concentrations of purine nucleotides and purine and pyrimidine bases in cerebrospinal fluid of neurologically healthy children.

The concentrations of the nucleotides AMP and IMP, the nucleosides adenosine, guanosine and inosine, the purine bases adenine, guanine, hypoxanthine and xanthine, urate, and the pyrimidine bases cytosine, thymine and uracil were determined by high performance liquid chromatography in the cerebrospinal fluid of 63 children aged between 1 month and 13 years who showed no sign of neurological disease. The results are compared with those of other authors, and used to establish reference ranges for the above metabolites in the cerebrospinal fluid of children.

Adolescent↗