The 844ins68 cystathionine beta-synthase and C677T MTHFR gene polymorphism and the vaso-occlusive event risk in sickle cell disease

Introduction: Sickle cell disease (SCD) is an inflammatory condition with an increase in the adhesion of sickled erythrocytes, and it is a potential cause of vaso-occlusive episodes, an event related to clinical manifestations, morbidity and mortality. The cystathionine beta-synthase enzyme gene (CBS) and the methylenetetrahydrofolate reductase enzyme gene (MTHFR) are risk factors for thromboembolic disorders. This study evaluated the frequency of the 844ins68 CBS and C677T MTHFR gene polymorphisms and their possibility to be risk factors for vaso-occlusive crises.Material and methods: In total 91 blood samples from SCD patients were studied by PCR-RFLP and PCR-allele-specific, for the SCD genotype confirmation and polymorphism identification.Results: The presence of clinical manifestations related to vaso-occlusive crises were more frequent among patients with the Hb SS genotype (p = 0.007). The CBS enzyme gene was three times more frequent (p = 0.011) among patients with vaso-occlusive complications. The MTHFR gene mutation frequency showed no increased risk for vaso-occlusive crises in SCD patients (p = 0.193). The interaction between the two polymorphisms was evaluated in 12.08% of the SCD patients and doubled the vaso-occlusive disease risk (relative risk: 2.16).Conclusions: We conclude that the presence of 844ins68 CBS and C677T MTHFR gene polymorphism was a risk factor for vaso-occlusive episodes in the SCD patients evaluated.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Twenty years of neonatal screening for sickle cell disease in Brazil : the challenges of a continental country with high genetic heterogeneity

Sickle cell disease (SCD) is the most common inherited hematological disease worldwide. The benefits of diagnosis and early intervention have led to the wide dissemination of public health programs worldwide. Through neonatal screening programs, it is possible to reduce morbidity and mortality in the first 5 years of life. The prophylactic use of penicillin, the anti-pneumococcal vaccine and other intensive care, increase the survival and quality of life of people with SCD. The aim of this study is to present the 20-year history of screening for hemoglobinopathies in Brazil and its challenges. From 2001 to 2019, an average of 2,400,000 children were screened per year nationwide, with the coverage being of 82,16%. The screening of 54,9% of newborns is collected up to their 5th day of life. The prevalence of SCD was 1:2,263 newborns; therefore, it was the second most-common disease detected by the program of Brazil, being only after hypothyroidism (1/2,175 live births). The healthcare system should provide the necessary infrastructure to confirm the diagnosis of newborns and to provide appropriate counseling and treatment. The early diagnosis and treatment, as well as the follow-up with a multidisciplinary team, are fundamental to the survival rate and the quality of life of patients

Avaliação eletroforética, cromatográfica e molecular da Hb D Los Angeles no Brasil

A variante de hemoglobina (Hb) D mais comum, Hb D Los Angeles ou D Punjab, é originada de uma transversão GAA->CAA no códon 121 da globina beta; essa mutação resulta na substituição do ácido glutâmico por glutamina na proteína. É a terceira variante de hemoglobina mais freqüente da população brasileira. Como as hemoglobinas D apresentam migração similar à hemoglobina S em pH alcalino, e com a hemoglobina A em pH ácido, são necessários vários testes para o correto diagnóstico. No presente estudo objetivou-se relacionar os diferentes procedimentos laboratoriais de rotina diagnóstica, além da análise molecular, para estabelecer o perfil de Hb D Los Angeles no Brasil. Foram analisados 47 indivíduos da população brasileira com provável Hb D Los Angeles, por vários procedimentos eletroforéticos em diferentes condições de pH, além da cromatografia líquida de alta pressão, e testes moleculares para confirmação da mutação. Foram encontrados quatro tipos de combinações de hemoglobinas: 42 indivíduos portadores de hemoglobina AD Los Angeles, dois indivíduos com doença de Hb S/D Los Angeles, dois indivíduos com Hb D Los Angeles e talassemia beta e um indivíduo com Hb D Los Angeles e Hb Lepore. Os indivíduos heterozigotos para D Los Angeles são assintomáticos, entretanto, em associação com outras variantes e talassemias podem apresentar graus variáveis de manifestações clínicas. Os resultados apresentados enfatizaram a necessidade da associação de várias metodologias para a identificação da Hb D Los Angeles, além de auxiliar na elucidação de combinações raras.<br>The most common Hb D variant, the Hb D-Los Angeles, also know as Hb D-Punjab, originates through a GAA->CAA change at the 121 codon of the beta globin gene; this mutation results in the replacement of glutamic acid for glutamine in the protein. It is the third most common hemoglobin variant in the Brazilian population. This variant has electrophoretic migration in alkaline pHs similar to Hb S and identical migration to hemoglobin A in acidic pHs. Thus, several techniques are necessary for its correct diagnosis. The purpose of this work was to relate the different laboratorial techniques and molecular analyses to determine the profile of Hb D Los Angeles in Brazil. Forty-seven individuals from the Brazilian population with Hb D Los Angeles were studied. Multiple electrophoresis in several experimental conditions were carried out, in addition to high performance liquid chromatography (HPLC) and molecular analysis to confirm this mutation. Four compound heterozygotes were observed: 42 individuals heterozygous Hb AD Los Angeles, two with Hb S/D Los Angeles disease, two individuals with Hb D Los Angeles and beta-thalassemia and one with Hb D Los Angeles and Hb Lepore. The heterozygous hemoglobin D Los Angeles is asymptomatic, even though its association with other variants and thalassemias may present varying degrees of clinical manifestations. The results presented emphasize the significance of the association of different laboratorial techniques for D Los Angeles diagnosis, and help to elucidate rare combinations

Low-level laser therapy of leg ulcer in sickle cell anemia

Submitted by Guilherme Lemeszenski ([email protected]) on 2013-08-22T18:40:41Z No. of bitstreams: 1 S1516-84842012000100018.pdf: 407297 bytes, checksum: 63c902afadbe505a41dfa1c96100b8f0 (MD5)Made available in DSpace on 2013-08-22T18:40:41Z (GMT). No. of bitstreams: 1 S1516-84842012000100018.pdf: 407297 bytes, checksum: 63c902afadbe505a41dfa1c96100b8f0 (MD5) Previous issue date: 2012-01-01Made available in DSpace on 2013-09-30T19:26:39Z (GMT). No. of bitstreams: 2 S1516-84842012000100018.pdf: 407297 bytes, checksum: 63c902afadbe505a41dfa1c96100b8f0 (MD5) S1516-84842012000100018.pdf.txt: 10160 bytes, checksum: 511ff8f7834570735e99fde8d5bc9b06 (MD5) Previous issue date: 2012-01-01Submitted by Vitor Silverio Rodrigues ([email protected]) on 2014-05-20T14:00:35Z No. of bitstreams: 2 S1516-84842012000100018.pdf: 407297 bytes, checksum: 63c902afadbe505a41dfa1c96100b8f0 (MD5) S1516-84842012000100018.pdf.txt: 10160 bytes, checksum: 511ff8f7834570735e99fde8d5bc9b06 (MD5)Made available in DSpace on 2014-05-20T14:00:35Z (GMT). No. of bitstreams: 2 S1516-84842012000100018.pdf: 407297 bytes, checksum: 63c902afadbe505a41dfa1c96100b8f0 (MD5) S1516-84842012000100018.pdf.txt: 10160 bytes, checksum: 511ff8f7834570735e99fde8d5bc9b06 (MD5) Previous issue date: 2012-01-01Universidade Estadual Paulista Júlio de Mesquita Filho Biology Department Laboratory of Hemoglobin and Genetics of Hematological DiseasesFaculdade de Medicina de São José do Rio Preto (FAMERP) Physiotherapy DepartmentUniversidade Estadual Paulista Júlio de Mesquita Filho Biology Department Laboratory of Hemoglobin and Genetics of Hematological Disease

O processo de consentimento livre e esclarecido nas pesquisas em doença falciforme

Resumo Doença falciforme diz respeito a grupo de hemoglobinopatias associadas à presença da hemoglobina S. Sendo majoritária na população negra, e acometendo em sua maioria vulneráveis e vulnerados, a forma homozigota da doença — a anemia falciforme — é considerada relevante problema de saúde pública no Brasil. Entendendo a pesquisa científica como essencial para a promoção da saúde e para melhorar a qualidade de vida dos pacientes, o processo de consentimento livre e esclarecido deve ser aplicado para superar, na medida do possível, vulnerabilidades a que as pessoas com doença falciforme estão expostas. Recursos lúdicos, transmissão coletiva de informações, proteção conferida pelas associações de pacientes e a formação permanente em ética em pesquisa por parte dos profissionais que aplicam o consentimento são indicados como ferramentas para otimizar esse processo