Triagem neonatal de deficiência de glicose-6-fosfato desidrogenase e prevalência das mutações G202A (G6PD A-) e C563T (G6PD Mediterrâneo) em Mato Grosso/Brasil / Neonatal Screening for glucose-6-phosphate dehydrogenase deficiency and prevalence of G202A (G6PD A-) and C563T (G6PD mediterranean) mutations in Mato Grosso / Brazil

Objetivos: A deficiência de glicose-6-fosfato desidrogenase (G6PD) está associada a um maior risco de encefalopatia bilirrubínica e de crise hemolítica aguda grave desencadeada por drogas como a primaquina e a dapsona. Conhecer a prevalência dessa deficiência enzimática em área onde a malária e a hanseníase ainda estão presentes e conhecer a prevalência das principais mutações traz subsídios para planejamento de estratégias com vistas à redução de riscos associados a esta deficiência enzimática. Métodos: Estudo descritivo transversal conduzido em uma região do centro-oeste do Brasil. Exame de triagem para deficiência de G6PD foi realizado em 3573 recémnascidos. Exame confirmatório foi necessário em 188 crianças triadas como possíveis portadores de deficiência. Nas crianças em que foi confirmada a deficiência de G6PD foi feita pesquisa das mutações G202A (G6PD A-) e C563T (G6PD Mediterrâneo) por PCR. Resultados: A deficiência de G6PD foi confirmada em 63 crianças, sendo 60 meninos (95,2%) e três meninas (4,8%). O percentual de exames falso-positivos na fase de triagem foi de 66,5%, estando o percentual de falso-positivos associado à temperatura e tempo de transporte das amostras. Entre as crianças que confirmaram deficiência de G6PD, foi mais frequente a história de anemia em familiares e de icterícia neonatal. Houve associação entre hematócrito baixo e deficiência enzimática, mas não com hemoglobina, contagem de reticulócitos ou neutrófilos. A prevalência da deficiência de G6PD (IC95%) foi de 1,76% (1,37; 2,24) entre os recém-nascidos triados e de 3,34% entre os meninos (2,58; 4,25). A mutação C563T não foi identificada em nenhuma criança, mas a mutação G202A estava presente em 58 crianças - 92,06% (IC95%: 83,29 - 97,03): 56/60 meninos e em 2/3 meninas homozigotas. Foi identificado um menino com Kernicterus portador da mutação G202A em hemizigose. Conclusão: O elevado percentual de falso-positivos na etapa de triagem, o tempo necessário entre coleta...

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with an increased risk of bilirubin encephalopathy in neonates and acute hemolytic crisis triggered by drugs such as primaquine and dapsone. In an area where malaria and Hansen's disease are still present, knowing the prevalence of this enzyme defect and determining the prevalence of major mutations is important for planning strategies for reducing the risks associated with this enzyme deficiency. Methods: Sectional study was conducted in a Midwestern region of Brazil. Screening for G6PD deficiency was performed in 3,573 neonates. Confirmatory tests were necessary for 188 positively screened children. After confirmation, PCR investigation was utilized to identify the mutations. Results: G6PD deficiency was confirmed in 63 children: 60 boys (95.2%) and 3 girls (4.8%). The percentage of false-positive cases in the screening phase, 66.5% and was associated with the temperature and transportation time of the samples. Family history of anemia and jaundice was more frequent among the children with confirmed G6PD deficiency. An association between a low hematocrit and enzyme deficiency was observed. However, there was no association with hemoglobin reticulocyte or neutrophils counts. The prevalence of G6PD deficiency (CI95%) was 1.76% (1.37; 2.24) among all screened neonates and 3.34% (2.58; 4.25) among male children. The C563T mutation was not identified in any child. The G202A mutation was present in 58 children - 92.06% (CI95%: 83.29 - 97.03), 56/60 boys and 2/3 homozygous girls. One boy with a hemizygous G202A mutation was identified as having Kernicterus. Conclusion: The high percentage of false-positive results when first screening for G6PD deficiency; the long delay time between the test and result; along with the high cost of the this screening test, are all factors that do not support adding this test to the already established Brazilian neonatal screening programs. The prevalence...

An historical and clinical review of the interaction of leprosy and pregnancy: a cycle to be broken.

Since earliest history the person with leprosy has been shut out from society. Laws have prohibited marriage and allowed divorce of those with leprosy. Segregation of the sufferer from the rest of society has been followed by separation of the sexes, and of leprous parents from their children. With the advent of antileprotic drugs, first dapsone then multidrug therapy (MDT), infection can be treated, individuals made non-infectious, and the pool of infection in the community reduced. The clinical signs of leprosy are due not to the degree of infection but to the immunological status of the host. Hormonal changes at puberty and in pregnancy can cause variation of the host's immune status. Pregnancy in women with leprosy is a hazardous undertaking. First appearance of leprosy, reactivation of the disease and relapse in 'cured' patients is likely to occur particularly in the third trimester of pregnancy. Leprosy reactions caused by variation in cell mediated and humoral immunity are triggered off by pregnancy: type 1 reaction (reversal reaction, RR) occurs post partum, while type 2 reaction (erythema nodosum leprosum, ENL) peaks in late pregnancy. Both types of reaction continue long into lactation. Neuritis with loss of both sensory and motor function is associated with relapse and reaction. Relapse, reaction and nerve damage, especially 'silent neuritis', with subsequent deformity and disability, occur not only in women on apparently effective treatment but also in those who have received MDT and have been released from treatment (RFT). To prevent disability, research is urgently needed into the mechanisms of early and late reaction and neuritis. Pregnancy is not only a trigger factor for reaction but an ideal in vivo model for research. Up to 20% of children born to mothers with leprosy may develop leprosy by puberty. While early leprosy in young children is self-healing, when marriage and childbearing take place at an early age the daughters of mothers with leprosy are likely to run the risk of experiencing the adverse effects of pregnancy on leprosy. Increased awareness and health education, as well as long term surveillance of 'cured' leprosy patients, are essential to break a potentially vicious cycle of leprosy and pregnancy. Women with cured leprosy could play an important role in screening for and detection of both early leprosy in children and late, post-MDT RFT, nerve damage in their mothers.