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, Wilcoxon's test, and McNemar's 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.

Clinical profile and molecular characterization of Galactosemia in Brazil: identification of seven novel mutations.

BACKGROUND: Classical Galactosemia (CG) is an inborn error of galactose metabolism caused by the deficiency of the galactose-1-phosphate uridyltransferase enzyme. It is transmitted as an autosomal recessive disease and is typically characterized by neonatal galactose intolerance, with complications ranging from neonatal jaundice and liver failure to late complications, such as motor and reproductive dysfunctions. Galactosemia is also heterogeneous from a molecular standpoint, with hundreds of different mutations described in the GALT gene, some of them specific to certain populations, reflecting consequence of founder effect. METHODS: This study reviews the main clinical findings and depicts the spectrum of mutations identified in 19 patients with CG, six with Duarte Galactosemia and one with type 2 Galactosemia in Brazil. Some individuals were diagnosed through expanded newborn screening test, which is not available routinely to all newborns. RESULTS: The main classical Galactosemia mutations reported to date were identified in this study, as well as the Duarte variant and seven novel mutations - c.2 T > C (p.M1T), c.97C > A (p.R33S), c.217C > T (p.P73S), c.328 + 1G > A (IVS3 + 1G > A), c.377 + 4A > C (IVS4 + 4A > C), c.287_289delACA (p.N97del) and c.506A > C (p.Q169P). This was expected, given the high miscegenation of the Brazilian population. CONCLUSIONS: This study expands the mutation spectrum in GALT gene and reinforces the importance of early diagnosis and introduction of dietary treatment, what is possible with the introduction of Galactosemia in neonatal screening programs.

[Hyperammonemia secondary to the use of valproic acid: case report]. / Hiperamonemia secundária ao uso terapêutico de acido 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.

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.

[Neonatal screening program at the university hospital of the Ribeirão Preto School of Medicine, São Paulo University, Brazil]. / 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 program's mean coverage during this period was 94.5%. There was major improvement in the parameters for evaluating the program's quality, although they were still far from ideal. Public-awareness campaigns on the importance of neonatal screening are needed to increase the program's 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.

Erros inatos do metabolismo confirmados no Hospital das Clínicas de Ribeirão Preto-SP no período de 2000 a 2008 / Inborn errors of metabolism in the Hospital of Clinics of Ribeirão Preto - SP from 2000 to 2008

Os Erros Inatos do Metabolismo (EIM) vêm sendo cada vez mais identificados nos últimos anos. A preocupação com o diagnóstico precoce decorre do foco na prevenção de deficiências, especialmente a mental. Este estudo descritivo teve por objetivo verificar diagnósticos confirmados e modalidades de tratamento utilizadas de janeiro de 2000 a dezembro de 2008. Método: foi realizada busca ativa de casos confirmados nos serviços que atendem esse tipo doença: neurologia (neuropediatria e doençasneuromusculares), pediatria (serviço de gastrologia e hepatologia) e genética clínica, além de levantamento no Serviço de Arquivo Médico do HCFMRP-USP. Foram confirmados 165 pacientes com EIM, com idades de um dia a 22 anos (mediana de um ano); 50 casos foram defeitos na síntese ou catabolismo de moléculas complexas, 65 no metabolismo intermediário, e 50 na produção ou utilização de energia. O tratamento foi instituído para 12 dos 50 pacientes do grupo I sendo reposição enzimática em 11 e transplante de medula óssea em um; todos do grupo II e III receberam orientação nutricional; 60 do grupo II receberam fórmula dietética industrializada; dos 50 do grupo III, 43 com mitocondriopatias receberam L-carnitina e coenzimas e aqueles com glicogenose, orientação sobre aporte de carbohidratos. A formação de novos recursos humanos, integração com a Rede EIM Brasil e linhas de pesquisa na área são prioridades para melhorar a acuidade na detecção e tratamento de erros inatos do metabolismo.

Inborn Errors of Metabolism have been increasingly identified in recent years. The early diagnosis focuses on prevention of disabilities, especially mental retardation. This descriptive study aims to verify confirmed diagnosis and treatment modalities in HCFMRP-USP cases from January of 2000 to December of 2008. A total of 165 patients with ages ranging from one day to 22 years (median one year) were detected. Fifty patients had synthesis or catabolism of complex molecules (group I), 65 intermediary metabolism (group II), and 50 had production or use of energy (group III) defects. Among the patients of group I, 11 had enzyme replacement therapy, and one bone marrow transplantation; for group II and III, inaddition to daily nutritional guidance for all of the patients, 60 from group II received industrialized diets; from group III, 43 with mitochondrial diseases received L-carnitine and coenzymes, and those with glycogenosis were focused mainly on the intake of carbohydrates. New human resources, integration with the Network EIM Brazil and lines of research in the area are priorities for improving the accuracy in the detection and treatment of inborn errors of metabolism.

Programa de Triagem Neonatal do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brasil / Neonatal Screening Program at the University Hospital of the Ribeirao Preto School of Medicine, São Paulo University, Brazil

O Programa de Triagem Neonatal do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brasil, instituído em 1994 diagnosticou, até 2005, 76 crianças com hipotireoidismo congênito, 10 com fenilcetonúria e 25 com hemoglobinopatias, o que representou uma incidência de 1:2.595, 1:19.409, 1:4.120, respectivamente. Foram diagnosticadas 2.747 crianças com traço falciforme (1:37,5 nascidos vivos). A cobertura média do programa foi de 94,5 por cento. Houve uma considerável melhora nos parâmetros de avaliação da qualidade do programa no período, porém, sem atingir os índices ideais. Campanhas visando à maior divulgação da importância da triagem neonatal são necessárias para aumentar a cobertura e a instituição do 3º dia de vida do recém-nascido como sendo o Dia do Teste do Pezinho poderia contribuir para que idades mais precoces de tratamento fossem atingidas, melhorando o prognóstico das crianças acometidas.

The Neonatal Screening Program at the University Hospital of the Ribeirao 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 program's mean coverage during this period was 94.5 percent. There was major improvement in the parameters for evaluating the program's quality, although they were still far from ideal. Public-awareness campaigns on the importance of neonatal screening are needed to increase the program's 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.

Hiperamonemia secundária ao uso terapêutico de ácido valpróico: relato de caso / Hyperammonemia secondary to the use of valproic acid: case report

O ácido valpróico tem sido amplamente utilizado no tratamento da epilepsia, sendo usualmente bem tolerado, não obstante alguns efeitos colaterais que lhe são atribuídos. Um efeito ainda pouco conhecido é a hiperamonemia, independente da hepatotoxicidade da droga. A hiperamonemia se estabelece no início ou no decurso do tratamento, sendo caracterizada por vômitos, alteração progressiva da consciência, sinais neurológicos focais e aumento na freqüência das crises epilépticas. Descrevemos o caso de menino de seis anos de idade que desenvolveu hiperamonemia pelo uso terapêutico de ácido valpróico. Os exames descartaram aminoacidopatias, acidemias orgânicas e distúrbios do ciclo da uréia, sendo a hipótese de efeito secundário reiterada pela normalização da concentração sangüínea de amônia, após a retirada do medicamento. Os mecanismos da hiperamonemia são discutidos, concluindo-se que o monitoramento da amônia é importante nos pacientes que utilizam o ácido valpróico.

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

Um caso raro de meningite recorrente devido a meningocele sacral anterior e agenesia das vértebras sacras é descrito. Herança autossômica dominante para malformaçao medular caudal é demonstrada e, possíveis fatores ambientais (ligados ao cromo), sao discutidos.

Paralisia cerebral diagnóstico etiológico / Cerebral palsy aetiologic diagnosis

Em estudo retrospectivo foram analisados 35 prontuários, obtidos ao acaso, de crianças com diagnóstico de Paralisia Cerebral (PC), atendidas no Hospital das Clínicas de Ribeirão Preto, entre 1982 e 1998, com o objetivo de verificar fatores etiológicos. As infecções congênitas (36 por cento) e agressão hipóxico-isquêmica (28 por cento) foram os mais freqüentes fatores determinantes de PC entre 25 casos com etiologia definida. Estes achados podem ser utilizados para estratégias regionais de prevenção de deficiências. Para os casos sem etiologia definida, lembram-se as formas herdadas de paralisia cerebral e o diagnóstico diferencial com doenças degenerativas