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. © 2009.link_to_subscribed_fulltex

Avaliação econômica em saúde: triagem neonatal da galactosemia Newborn screening for galactosemia: a health economics evaluation

Este trabalho avalia a eficiência da adição do exame da galactosemia junto ao Teste do Pezinho. Baseado na incidência média estimada de galactosemia, de 1:19.984 recém-nascidos, no Estado de São Paulo, Brasil, este estudo desenvolve um modelo de análise de custo-benefício, utilizando a relação benefício/custo (B/C), a taxa de juros de 9,25% ao ano para descapitalização dos resultados obtidos. Também se realiza uma análise de sensibilidade, em função da variação da taxa de juros entre 0 e 20% e do intervalo de 95% de confiança da incidência da galactosemia (1:7.494 a 1:59.953 recém-nascidos). A economia obtida com a melhora da saúde das crianças doentes identificadas precocemente é superior aos custos (B/C = 1,33), caracterizando como eficiente a política de adição do exame neonatal para galactosemia no Teste do Pezinho. Quanto menor a taxa de juros vigente na economia, mais eficiente é a política de triagem neonatal, não considerados os custos sociais intangíveis evitados.<br>This study assesses the efficiency of the galactosemia add-on test in neonatal screening performed on regular Guthrie card blood spots. Based on estimated average incidence of galactosemia (1:19,984 newborns) in São Paulo State, Brazil, the study develops a cost-benefit analysis model, using a B/C ratio and a 9.25% annual interest rate in order to decapitalize the results. Sensitivity analysis is also performed, varying (as a function of the interest or discount rate) from 0 and 20% and according to the 95% confidence interval (1:7,494-1:59,953 newborns). The results show that the savings obtained by improved health of galactosemic patients detected early by add-on neonatal screening is superior to the costs (B/C=1.33), characterizing galactosemia add-on testing in neonatal screening as an efficient policy. The lower the prevailing interest rate in the economy, the more efficient the neonatal screening policy

Crescimento de prematuros de extremo baixo peso nos primeiros dois anos de vida Growth of extremely low birth weight infants during the first two years of life

OBJETIVO: Analisar o padrão de crescimento de prematuros de extremo baixo peso (EBP) até 24 meses de idade corrigida, a influência da displasia broncopulmonar (DBP) e os fatores de risco para falha de crescimento. MÉTODOS: Coorte de prematuros <1.000g de gestação única, nascidos e acompanhados em um centro terciário. O crescimento foi avaliado por meio de escores-z para peso, comprimento e perímetro cefálico ao nascimento, com 40 semanas, aos 3, 6, 12, 18 e 24 meses de idade corrigida. Dentre 81 sobreviventes, 70 foram estudados e estratificados em dois grupos: DBP (n=41) e sem DBP (n=29). Foi realizada análise bivariada com teste t ou Mann-Whitney, qui-quadrado ou Exato de Fisher, e análise multivariada com regressão logística. RESULTADOS: Em ambos os grupos, o escore-z de peso diminuiu significantemente entre o nascimento e 40 semanas. Houve um pico de incremento nos escores-z de peso, comprimento e perímetro cefálico entre 40 semanas e três meses. No grupo sem DBP, os escores-z atingiram a faixa normal a partir dos seis meses e assim permaneceram até 24 meses de idade corrigida. Crianças com DBP tiveram menores escores-z de peso e perímetro cefálico no primeiro ano, mas equipararam-se às sem DBP no segundo ano de vida. A regressão logística mostrou que catch-down no escore-z de peso com 40 semanas foi fator de risco para falha de crescimento. CONCLUSÕES: Prematuros EBP apresentam catch-up precoce do crescimento nos primeiros dois anos. Crianças com DBP têm pior crescimento ponderal. A restrição do crescimento pós-natal prediz a falha de crescimento nos primeiros anos.<br>OBJECTIVE: To evaluate the growth pattern of extremely low birth weight infants(ELBW) from birth to 24 months of adjusted gestational age (AA), the influence of bronchopulmonary dysplasia (BPD) and risk factors associated to growth failure. METHODS: This cohort study included all singleton inborn infants with birthweight <1,000g, admitted in the follow-up clinic of a level III Perinatal Center. Weight, length and head circumference were measured at birth, 40 weeks, and 3, 6, 9, 12, 18, 24 months AA, and Z-scores were calculated. Out of the 82 survivors, 70 were studied and classified in two groups: BPD (n=41) and no-BPD (n=29). Statistical analysis included t-test or Mann-Withney, chi-square or Fisher Exact test, and multivariate logistic regression. RESULTS: In both groups, weight z-score decreased significantly between birth and 40 weeks AA. A peak incremental change in weight, length and head circumference z-scores occurred between 40 weeks and three months. Z-scores for the no-BPD group were close to the expected values by the age of six months and remained at these levels at 24 months AA. Children with BPD had lower z-scores for weight and head circumference in the first year of life, but no difference was found between BPD and no-BPD children in the second year of life. Regression analysis showed that catch-down in weight z-score at 40 weeks was a risk factor for failure to thrive. CONCLUSIONS: ELBW infants experienced early catch-up growth during the first two years of life. ELBW with BPD had poor weight gain. Post-natal growth restriction predicts failure to thrive in infancy

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups Results From the Randomized CREDENCE Trial

BACKGROUND: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). METHODS: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. RESULTS: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). CONCLUSIONS: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02065791