Marlene de Fátima Turcato

Functional deficiencies of sulfite oxidase: Differential diagnoses in neonates presenting with intractable seizures and cystic encephalomalacia

Sulfite oxidase is a mitochondrial enzyme encoded by the SUOX gene and essential for the detoxification of sulfite which results mainly from the catabolism of sulfur-containing amino acids. Decreased activity of this enzyme can either be due to mutations in the SUOX gene or secondary to defects in the synthesis of its cofactor, the molybdenum cofactor. Defects in the synthesis of the molybdenum cofactor are caused by mutations in one of the genes MOCS1, MOCS2, MOCS3 and GEPH and result in combined deficiencies of the enzymes sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. Although present in many ethnic groups, isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are rare inborn errors of metabolism, which makes awareness of key clinical and laboratory features of affected individuals crucial for early diagnosis. We report clinical, radiologic, biochemical and genetic data on a Brazilian and on a Turkish child with sulfite oxidase deficiency due to the isolated defect and impaired synthesis of the molybdenum cofactor, respectively. Both patients presented with early onset seizures and neurological deterioration. They showed no sulfite oxidase activity in fibroblasts and were homozygous for the mutations c.1136A>G in the SUOX gene and c.667insCGA in the MOCS1 gene, respectively. Widely available routine laboratory tests such as assessment of total homocysteine and uric acid are indicated in children with a clinical presentation resembling that of hypoxic ischemic encephalopathy and may help in obtaining a tentative diagnosis locally, which requires confirmation by specialized laboratories.

Programa de Triagem Neonatal do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brasil

The Neonatal Screening Program at the University Hospital of the Ribeirão Preto School of Medicine, São Paulo University, Brazil, was introduced in 1994. As of December 2005, congenital hypothyroidism had been diagnosed in 76 infants, phenylketonuria in 10, and hemoglobinopathies in 25, representing incidence rates of 1:2,595, 1:19,409, and 1:4,120, respectively. A total of 2,747 newborns had the sickle cell trait, i.e., were heterozygous for the sickle mutation (1:37.5 live births). The programs mean coverage during this period was 94.5%. There was major improvement in the parameters for evaluating the programs quality, although they were still far from ideal. Public-awareness campaigns on the importance of neonatal screening are needed to increase the programs coverage. Setting postnatal day 3 as the standard Day for the Heel Stick Test would help ensure treatment at earlier ages, thus improving prognosis for affected infants.O Programa de Triagem Neonatal do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Brasil, instituido em 1994 diagnosticou, ate 2005, 76 criancas com hipotireoidismo congenito, 10 com fenilcetonuria e 25 com hemoglobinopatias, o que representou uma incidencia de 1:2.595, 1:19.409, 1:4.120, respectivamente. Foram diagnosticadas 2.747 criancas com traco falciforme (1:37,5 nascidos vivos). A cobertura media do programa foi de 94,5%. Houve uma consideravel melhora nos parâmetros de avaliacao da qualidade do programa no periodo, porem, sem atingir os indices ideais. Campanhas visando a maior divulgacao da importância da triagem neonatal sao necessarias para aumentar a cobertura e a instituicao do 3o dia de vida do recem-nascido como sendo o Dia do Teste do Pezinho poderia contribuir para que idades mais precoces de tratamento fossem atingidas, melhorando o prognostico das criancas acometidas.

Recurrent meningitis in a case of congenital anterior sacral meningocele and agenesis of sacral and coccygeal vertebrae

A rare case of recurrent meningitis due to congenital anterior sacral meningocele and agenesis of the sacral and coccygeal vertebrae is described. An autosomal dominant inheritance is demonstrated for lower cord malformation, and environmental factors (chromic acid or fumes) are discussed.

Hiperamonemia secundária ao uso terapêutico de ácido valpróico: relato de caso

Valproic acid has been widely used for the treatment of epilepsy. Although it is usually well tolerated, it has been associated with some side effects. A poor studied side effect is the hyperammonemia, which independs from the drug hepatotoxic action. The hyperammonemia may occurs just after the beginning or during the treatment and is characterized by vomiting, progressive impairment of consciousness, focal neurologic signs and increased seizure frequency. We report boy a 6 year-old boy who presented with hyperammonemia during the use of valproic acid within the therapeutic range. Complementary investigation was negative for aminoacidopathy, organic acidemia and urea cycle disorders. The hypothesis of secondary effect to the valproic acid was reinforced by the normalization of ammonia levels after drug withdrawal. The pathogenesis of valproate-induced hyperammonemia have been discussed. We conclude that routine monitoring of ammonia blood concentration are strongly recommended in patients under valproic acid treatment.

Effects of Short-Term Calcium Supplementation in Children and Adolescents with Phenylketonuria

Reduction of bone mineral density and the risk of osteopenia have been reported to occur in phenylketonuria (PKU) patients. This study aimed to evaluate the short-term effects of calcium supplementation in phenylketonuric children and adolescents. The study included 18 patients with PKU aged 5-18 yr (61% male) under clinical and nutritional treatment. Evaluation of food intake, anthropometry, and biochemical and phalangeal quantitative ultrasound were performed before (phase 1) and after (phase 2) calcium supplementation (1000 mg/d) for 34 d. Statistical analysis was performed using t test for paired samples, Wilcoxons test, and McNemars test (p <0.05). There was an inadequate intake of phosphorus and vitamin D, the same occurring with serum concentrations of these nutrients. About 50% of the patients had an accumulation of adipose tissue measures, with a negative correlation between Z-score, body mass index, and phalangeal quantitative ultrasound (amplitude-dependent speed of sound [AD-SoS]). There was a significant difference in urinary phosphorus excretion with higher values before supplementation. Comparison of the two phases revealed significantly higher AD-SoS values after the supplementation (p = 0.017). The reduction in phosphorus excretion associated with increased AD-SoS between the two phases suggested increased bone formation, and showed no negative effects in relation to short-term calcium supplementation in children and in adolescents with PKU.