Hematological and molecular analysis of patients with G6PD deficiency revealed coexistent hereditary spherocytosis and alpha thalassemia

Abstract

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis (HS), and alpha thalassemia (α-thal) are frequent erythrocyte pathologies with different geographic distributions worldwide. Our aim is to report hematological and molecular findings of G6PD deficient Mexican patients in coinheritance with suggestive hereditary spherocytosis (sHS) and α-thal. Methods: We studied 78 G6PD deficiency patients. Hematological parameters, acidified glycerol lysis test, erythrocyte morphology, electrophoresis, and hemoglobin quantification were obtained. G6PD and HBA2/HBA1 variants were identified using ARMS-PCR, Gap-PCR, or Sanger sequencing.Results: Nine G6PD variants were identified; A -202A/376G , A -376G/968C , and A +376G as the most frequent. G6PD Santiago de Cuba 1339A and Kamiube 1387T were detected in Mexicans for first time. Hematological analysis revealed additional erythrocyte pathologies in 52 patients, 32 with positive osmotic fragility test and spherocytes in blood smear (suggestive hereditary spherocytosis, sHS), 12 with microcytosis and 8 with all three defects who had the most severe phenotype, with significantly lower hematological parameters (Hb, PCV, MCV, and MCH). α-thal variants (α Hph α, α -59C>T α and -α 3.7 ) were observed in 65% of patients with microcytosis. Conclusion:Additional erythrocyte defects were observed in 69.3% of G6PD deficiency patients. We stress the importance of searching for the presence of additional erythrocyte hereditary diseases in patients with G6PD deficiency.

Chronic hemolytic anemia associated to G6PD Canton aggravated by a KLF1 mutation

“…Notably, these mutations demonstrate that a single gene may not be able to explain all the current patient's clinical manifestations. Hemolysis attributable to G6PD deficiency is sometimes exacerbated by co-inherited genetic erythrocyte alterations, such as hereditary spherocytosis, 3 thalassemia, 3 pyruvate kinase (PK) deficiency, 4 and congenital dyserythropoietic anemia. 5 In some circumstances, the effects of two genetic disorders are simply additive, but a synergistic effect may also be observed, leading to more severe chronic hemolytic anemia.…”