RESUMO
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked disorder, is usually observed in hemizygote males and very rarely in females. The G6PD class 1 variants, very uncommon, are associated with chronic hemolytic anemia. Here we report a Portuguese woman who suffered in her sixties from a chronic hemolytic anemia due to G6PD deficiency. Molecular studies revealed heterozygosity for an in-frame 18-bp deletion, mapping to exon 10 leading to a deletion of 6 residues, 362-367 (LNERKA), which is a novel G6PD class 1 variant, G6PD Tondela. Two of her three daughters, asymptomatic, with G6PD activity within the normal range, are heterozygous for the same deletion. The patient's leukocyte and reticulocyte mRNA studies revealed an almost exclusive expression of the mutant allele, explaining the chronic hemolytic anemia. Patient whole blood genomic DNA HUMARA assay showed a balanced pattern of X chromosome inactivation (XCI), but granulocyte DNA showed extensive skewing, harboring the mutated allele, implying that in whole blood, lymphocyte DNA, with a very long lifetime, may cover up the current high XCI skewing. This observation indicates that HUMARA assay in women should be assessed in granulocytes and not in total leukocytes.
Assuntos
Anemia Hemolítica/genética , Glucosefosfato Desidrogenase/genética , Deleção de Sequência , Idoso , Anemia Hemolítica/enzimologia , Doença Crônica , Feminino , Granulócitos , Heterozigoto , Humanos , Fases de Leitura , Inativação do Cromossomo XAssuntos
Anemia Hemolítica Congênita não Esferocítica/genética , Piruvato Quinase/deficiência , Erros Inatos do Metabolismo dos Piruvatos/genética , Traço Falciforme/genética , Adulto , Anemia Hemolítica Congênita não Esferocítica/sangue , Anemia Hemolítica Congênita não Esferocítica/complicações , Criança , Índices de Eritrócitos , Feminino , Hemoglobina Falciforme/metabolismo , Heterozigoto , Humanos , Masculino , Mutação de Sentido Incorreto , Oxigênio/sangue , Fenótipo , Mutação Puntual , Piruvato Quinase/genética , Erros Inatos do Metabolismo dos Piruvatos/sangue , Erros Inatos do Metabolismo dos Piruvatos/enzimologia , Traço Falciforme/sangue , Traço Falciforme/complicações , Globinas beta/genéticaRESUMO
Hemoglobinopathies are priority genetic diseases for prevention programs in at-risk populations. We implemented an accurate and simple methodology to identify hemoglobin (Hb) variants and to quantify HbA2 and HbF in capillary blood samples stored at room temperature for up to 7 days after collection. This methodology is particularly indicated for screening for carriers in primary care medical centers in which facilities for collecting venous blood are not available.
