Hemoglobin EE disease in young Laotian children: Hematologic features and the contributions of genetic variations to Hb F expression

Abstract

AbstractBackgroundThe wide variation in hemoglobin (Hb) F levels has been observed in patients with Hb EE disease. This study aimed to describe hematologic features and determine the effect of genetic variants on Hb F expression in young children with Hb EE disease.MethodsHematologic features and Hb profiles of Laotian children aged 6–23 months, who originally enrolled in the Lao‐Zinc study, were retrospectively reviewed. Only children with Hb EE disease, as indicated by DNA analysis, were included in this current analysis. Genetic variants, including the Gγ‐XmnI polymorphism (C>T) of the HBG2 gene, the HBS1L‐MYB intergenic region on chromosome 6, and the BCL11A on chromosome 2 as well as the mutations occurring on the Krüppel‐like factor 1 (KLF1) gene, were examined.ResultsIn total, 205 children were diagnosed as having Hb EE disease with Hb F ranged from 1.2 to 43.7%. Most of the children had mild to moderate anemia with a remarkable microcytosis. Analysis of the genetic variants revealed an extremely high frequency of the Gγ‐XmnI (93.7%). Applying multiple regression analysis adjusted for age, sex, and α‐thal gene, a positive relation was observed for the rs4671393 (coefficient = 3.87, p = .005) and the rs2297339 (coefficient = 2.48, p = .046), but not the Gγ‐XmnI. A statistically non‐significant relation was noted for the rs9399137 and the −154 (C>T) KLF1 mutation.ConclusionOur findings provide insight into complex situation of Hb F variability in young children with Hb EE disease; and this can guide to appropriate care and counseling to affected families.