[Pyruvate dehydrogenase deficit associated to the C515T mutation in exon 6 of the E1alpha gene]. / Deficit de piruvato deshidrogenasa asociado a la mutacion C515T en el exon 6 del gen E1alpha.

INTRODUCTION: Pyruvate dehydrogenase (PDH) deficiency constitutes the most frequent metabolic origin of congenital lactic acidosis and is also responsible for a less usual form, found exclusively in females, which leads to a dysmorphic syndrome accompanied by severe cerebral malformations. The most common defect affects fraction E1alpha (gene Xp22.1-22.2). AIM: To report the case of a young female with PDH deficiency, dysmorphic syndrome, cerebral deformations and an unidentified mutation in the corresponding gene. CASE REPORT: An 8-month-old female with microcephaly, a narrow forehead, nasal hypoplasia, anteverted nostrils, thin lips, axial hypotonia, epileptic seizures and an umbilical hernia. Magnetic resonance imaging of the brain revealed intense supra- and infratentorial cortico-subcortical atrophy, ventricular dilatation and agenesis of the corpus callosum. Lactic and pyruvic acid concentrations were high both in blood and in cerebrospinal fluid (CSF), and the level of alanine was high in CSF. Muscular histology results were normal. PDH complex activity in fibroblasts and in muscle tissue, as well as that of the mitochondrial respiratory chain complexes in muscle homogenate, were found to be normal. A molecular genetic study of the gene for PDHE1alpha, both in formed elements in the blood and in fibroblasts, showed a C > T change in nucleotide 515 (C515T) of exon 6, which causes a P172L change in the protein. A study of 108 controls ruled out the possibility of a polymorphism. The parents did not have the mutation. CONCLUSIONS: The C515T mutation of exon 6 of the gene for PDH E1alpha is described. Normal activity of the PDH complex in fibroblasts and in muscle tissue does not exclude this condition.

[Galactosemia: the genotype and phenotype of seven patients]. / Galactosemia: genotipo y fenotipo de siete pacientes.

INTRODUCTION: Despite early dietary therapy, many patients with galactosemia show a neurodegenerative disease specially evident in speech impairment and movement disorders. Magnetic resonance imaging of the brain, show cerebral white matter changes with hypomielinization bilateral and symetrical periventricular hypersignal in T2. PATIENTS AND METHODS: We presented clinical and neuroradiological data of seven children (3 to 12 years of age) with classical galactosemia. All had a typical presentation in neonatal period. Two children had normal development (10 and 12 years-old), four presented developmental delay (10, 7, 4 and 3 years-old), and one showed a dystonic cerebral palsy (kernicterus). RESULTS: The brain MRI showed the typical involvement of white matter, in five children, and basal ganglia abnormalities in the kernicterus patient. Three patients are homozygous for Q188R mutation and two are compound heterozygous. CONCLUSION: We found a positive correlation among developmental delay, white matter involvement and Q188R mutation.

[Severe fulminant form of neonatal citrullinemia. Report of a case]. / Forma grave fulminante de citrulinemia neonatal. Comunicación de un caso.

INTRODUCTION: Citrullinemia is an autosomal recessive disease, which is caused by a deficiency of the argininosuccinate synthetase. The neonatal forms are serious and many times are associated with a high level of mortality. CASE REPORT: A newborn that came in again on her third day of life due to a apneic episodes which required mechanical ventilation. Previously, she rejected feeding, had poor suction, lethargy and remarkable hypoactivity. During the following hours, she showed serious neurologycal deterioration with multifocal convulsions and coma, passing away 20 hours after admission due to endocraneal hypertension. The metabolic evaluation confirmed very significant hyperammonemia, with important increase of citrullin and glutamin, and arginine in the low limits of normality. She was treated with sodium benzoate and arginine and she also needed exanguinotransfusion. It was not possible to put her on hemodyalisis. The findings of the autopsy confirmed massive cerebral edema and characteristic hystological changes in the liver. The determination of the enzymatical activity in liver tissue showed a partial deficiency, with a residual activity of 25% of the average control. CONCLUSIONS: This is a case of fulminant neonatal citrullinemia that we considered of interest in order to draw the attention of the clinical on this type of diseases. The prognosis depends on early diagnosis, witch is based on clinical suspicion and analytical determination of ammonia in every newborn with unexplained vomiting, lethargy or other symptoms of encephalopathy.

[Ornithine transcarbamylase deficiency. Biochemical studies in the diagnosis of 4 cases and the identification of carriers]. / Deficiencia de ornitina carbamil transferasa. Estudios bioquímicos realizados para el diagnóstico de cuatro casos y la identificación de portadores.

The biochemical studies for the diagnosis of four cases of OCT deficiency are described: two male sibs, with total enzymatic deficiency and neonatal death, and two symptomatic heterozygous females. The enzymatic activity was determined in hepatic necropsy or duodenal biopsy from these patients and carriers were identified among their relatives. The usefulness of the enzymatic analysis compared with the protein loading test followed by the determination of ammonia and orotic acid for the female carrier detection is discussed, and the interest of their identification to prevent the risk of hyperammonemic crisis with possible neurologic sequels is stressed.

[Sudden death of a patient with 3-hydroxy-3-methylglutaryl coenzyme A lyase deficiency]. / Muerte súbita en un paciente con deficiencia de 3-hidroxi-3-metilglutaril-coenzima A liasa.

A new case of neonatal 3-hydroxy-3-methylglutaric aciduria is described. 3-hydroxy-3-methylglutaryl CoA lyase activities in leukocytes demonstrated the patient's homozygosity and the heterozygous character of the parents and two other members of the family. Dietetic management with low fat high carbohydrate diet together with protein restriction and carnitine resulted in a good control of the metabolic acidosis, the hypoglycemia, and the physical and neurological development. Nevertheless, sudden death occurred at the age thirteen months without any previous apparent trouble and the necropsia showed neither signs of infection nor hepatic or cardiac derangement.

[Argininosuccinic aciduria. Comparative studies and detection of carriers in 3 affected families]. / Aciduria argininsuccínica. Estudios comparativos y detección de portadores en tres familias afectas.

Three patients with argininosuccinic aciduria are described. One of them is a neonatal form, with typical acute course and severe hyperammonemia who died on the sixth day of life. Postmortem analysis showed a marked plasmatic accumulation of argininosuccinic acid. Later on, red blood cell ASA-lyase levels demonstrated the heterozygosity of her parents and sisters. The two other patients are late onset forms and were diagnosed after detection of ASA and its anhydrides in plasma and urine. Levels of these metabolites did not correlate with levels of residual ASA-lyase in erythrocytes. Treatment with a hypoproteic diet supplemented with arginine has improved their clinical state. Carriers have been detected in both families. Importance of rapid diagnosis and treatment of hyperammonemic patients in order to prevent neurologic damage is emphasised.