Objective: To discuss the high prevalence of sickle cell disease in our environment and the increased morbidity and mortality as a result of infection associated with this condition. Sources of data:Review of MEDLINE from 1986 to 2003. We found around 600 references about the subject. Thirty-five journal articles were reviewed, in addition to chapters in two text books. Summary of the findings:We discuss general information concerning sickle cell disease as well as a few topics about the most frequently observed infections in these patients. Drug prophylaxis and immunizations are also covered.Conclusions: This review hopes to provide the pediatric community with information concerning the association between sickle cell disease and infections, so as to minimize the occurrence of complications.

The development of methodologies to identify the molecular lesions responsible for different types of beta-thalassemia has made it possible to correlate these data with clinical and hematological severity. We examined DNA from 35 patients with beta-thalassemia, residents of the State of São Paulo, Brazil, for some types of genetic modifying factors: beta-thalassemia mutations, the upstream Xmnl GY-globin gene polymorphisms, and alpha-globin gene deletions. Additionally, the beta-like gene cluster haplotypes and the presence of the AYT variant were studied. The following mutations were present in the 70 chromosomes studied: 54.3% codon 39 (C-->T) (beta degree); 18.6% IVS-I-6 (T-->C) (beta+); 18.6% IVS-I-110 (G-->A) (beta+), and 4.3% IVS-I-1 (G-->T) (beta degree). Haplotype II was associated with the nonsense mutation at codon 39, haplotype I with the IVS-I-110 and codon 39 mutations, and haplotypes VI and VII with the IVS-I-6 mutation. The Xmnl polymorphism was detected in three out of 31 patients studied. No alpha-thalassemia was detected among the thalassemia intermedia patients. The AYT variant was present in 87.1% of 31 thalassemia patients and was associated with the codon 39/haplotype II and IVS-I-6/haplotype VI mutations. This is the first study of the Brazilian population that has analyzed the beta-thalassemia mutations and other molecular variants, and has correlated them with the clinical manifestations.

Hb Köln was identified by DNA analysis in a Brazilian patient. A four-year old Brazilian female, with jaundice since birth, presented an abnormal band, between A2 and S, in hemoglobin electrophoresis on a cellulose acetate membrane, and a band with electrophoretic migration similar to Hb C on agar gel. Thermic instability and isopropanol precipitation tests were positive. Heinz bodies were observed in the patient’s peripheral blood. Sequencing of the three exons of the b globin gene detected a transition from G to A in the first position of codon 98. This alteration does not create or abolish any known restriction site. In this case, confirmation of the mutation was accomplished by allele-specific oligonucleotide hybridization, which is a simple and fast identification method when the clinical data and hematological and electrophoretic patterns are suggestive of Hb Köln.
Hb Köln resulta da substituição do aminoácido valina por metionina na posição 98 da cadeia da hemoglobina. Embora seja a mais freqüente das hemoglobinas instáveis, possui poucas características que permitem distinguíla sem a realização de análise estrutural da molécula. Com o objetivo de desenvolver um procedimento alternativo à análise protéica, este trabalho descreve a identificação da Hb Köln através de análise de DNA. Uma paciente branca, sexo feminino, 4 anos de idade, com icterícia desde o nascimento, foi analisada, apresentando uma banda anômala entre A2 e S em eletroforese em acetato de celulose, e migração eletroforética semelhante a Hb C em gel de agar. Os testes de instabilidade térmica e de precipitação pelo isopropanol foram positivos e foram observados corpúsculos de Heinz no sangue periférico. Os três exons do gene da globina foram seqüenciados e uma transição de G ® A foi identificada na primeira posição do codon 98. Essa alteração não cria ou abole nenhum sítio conhecido de enzima de restrição. Desta forma, a confirmação da mutação foi levada a efeito através de hibridização com oligonucleotídeos aleloespecíficos, o que permitiu o estabelecimento de um método simples e rápido de identificação de novos casos quando os dados clínicos e o padrão hematológico e eletroforético sugerem Hb Köln

This review hopes to provide the pediatric community with information concerning the association between sickle cell disease and infections, so as to minimize the occurrence of complications.

Este artigo é dedicado a Maria de Lourdes Santos Pardo -in memoriam.Artigo submetido em 16.01.04, aceito em 31.03.04. AbstractObjective: To discuss the high prevalence of sickle cell disease in our environment and the increased morbidity and mortality as a result of infection associated with this condition.Sources of data: Review of MEDLINE from 1986 to 2003. We found around 600 references about the subject. Thirty-five journal articles were reviewed, in addition to chapters in two text books. Summary of the findings:We discuss general information concerning sickle cell disease as well as a few topics about the most frequently observed infections in these patients. Drug prophylaxis and immunizations are also covered.Conclusions: This review hopes to provide the pediatric community with information concerning the association between sickle cell disease and infections, so as to minimize the occurrence of complications. ResumoObjetivo: A alta prevalência de anemia falciforme em nosso meio e a elevada morbimortalidade por infecções associada a esta condição estimularam a realização deste artigo de revisão. Síntese dos dados: Neste artigo, além de informações gerais a respeito da doença falciforme, são abordados alguns tópicos sobre as infecções mais freqüentemente observadas no paciente com anemia falciforme, assim como a profilaxia medicamentosa e imunizações disponíveis.Conclusões: Esta é uma revisão que visa fornecer à comunidade pediátrica informações sobre o binômio anemia falciforme e infecções, a fim de minimizar suas complicações nesta comunidade específica.

Embora estejam bem definidos os benefícios da implantação do programa de triagem neonatal para hemoglobinopatias, não são raros os estudos que apontam falhas nesses programas. Este estudo teve como objetivo avaliar o programa de triagem neonatal para hemoglobinopatias no município de Dourados, estado do Mato Grosso do Sul (MS). Foram entrevistadas, através da aplicação de formulários, 32 famílias cujos filhos foram identificados como portadores de hemoglobinopatias, durante a triagem neonatal, no período de janeiro de 2000 a dezembro de 2005. Adicionalmente, foram verificadas a cobertura do Programa Nacional de Triagem Neonatal (PNTN) e a incidência de hemoglobinopatias no MS, de 2000 a 2005. Dos 242 casos de hemoglobinopatias diagnosticados neste período, a heterozigose para hemoglobina S demonstrou incidência de 1,37%, a heterozigose para hemoglobina C, 0,37% e a heterozigose para hemoglobina D, 0,007%. Não foram diagnosticados casos de anemia falciforme. A cobertura encontrada foi de 81,4%. Foram detectadas falhas, como a não reconvocação para o exame confirmatório, ausência de encaminhamento médico para orientação, falta de investigação familiar e a falha na compreensão do aconselhamento genético. Rev. Bras. Hematol. Hemoter. 2010;32(2):126-130. Palavras-chave: Triagem neonatal; hemoglobinopatias; avaliação de programa.Some failures were detected such as not requiring patients to return for confirmation examinations, the lack of medical counseling and follow through, lack of investigations of family histories, and lack of understanding on the part of the family of the genetic counseling they received. Rev. Bras. Hematol. Hemoter. 2010;32(2):126-130.

BackgroundIn sickle cell disease, the quantification of Hb A2 is important for the differential diagnosis between sickle cell anemia (Hb SS) and Hb S/β0-thalassemia.ObjectiveTo determine Hb A2 levels as quantified by high performance liquid chromatography in patients with sickle cell anemia (Hb SS) and with the SC hemoglobinopathy, with or without concomitant alpha thalassemia.MethodsThis is a retrospective study of 242 children aged between two and six years with diagnoses of Hb SS or Hb SC. The hemoglobin was evaluated using high performance liquid chromatography and alpha thalassemia [3.7 kb deletion (−α3.7)] was detected by polymerase chain reaction. Patients were classified as homozygous (−α3.7/−α3.7), heterozygous (−α3.7/α), or homozygous wild-type. Analysis of variance was used to compare the mean Hb A2 values between the alpha thalassemia groups.ResultsThe mean (± standard deviation) Hb A2 concentrations in the Hb SS group (n = 135) was 3.68 ± 0.65%. The mean values for individuals with Hb SS and heterozygous (n = 28) or homozygous for alpha thalassemia (n = 3) were 3.98 ± 0.64% and 4.73 ± 0.25%, respectively. The mean Hb A2 of all the Hb SC patients (n = 107) was 4.01 ± 0.507 with 4.29 ± 0.41% and 4.91 ± 0.22% in individuals heterozygous (n = 23) and homozygous for alpha thalassemia (n = 7), respectively. All patients homozygous for alpha thalassemia had Hb A2 levels above 3.5%. However, Hb A2 values above 5.2% were seen in patients with Hb SS and Hb SC, independently of alpha thalassemia.ConclusionHb A2 levels are elevated in patients with Hb S or Hb C, and are directly influenced by the alpha thalassemia genotypes.

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