LAUSR

Hemoglobin (Hb) E (HBB:c.79G>A)/β-thalassemia disease is the most common thalassemia syndrome in Southeast Asian countries with a high prevalence of Hb E. Even though patients could present with a wide spectrum of clinical severity, the disease accounts for half of the severe β-thalassemia patients worldwide [1]. Among individuals with a carrier state of β-thalassemia or Hb E and homozygous Hb E who could be at-risk couples for Hb E/β-thalassemia, individuals with Hb E/ β-thalassemia themselves, especially with mild severity, may still be able to have their own children and also could be at-risk couples. The problem could occur with few Hb E/β-thalassemia compound heterozygotes who have a very low Hb F phenotype and could be misdiagnosed with Hb E homozygote by Hb analysis [2–4]. Consequently, if their spouses had inherited Hb E allele, they could be at-risk couples for Hb E/β-thalassemia. To date, there are no data regarding the frequency of Hb E/β-thalassemia cases with a low Hb F phenotype in real-life prenatal control situations. Our study was conducted prospectively in prenatal control program for β-thalassemia in the lower north of Thailand, between February 2014 and May 2017. All couples with a phenotypic diagnosis of homozygous Hb E by high-performance liquid chromatography (HPLC: VARIANTTM) in one person, and heterozygous or homozygous Hb E in the other, were recruited. Phenotypic diagnosis of Hb E homozygote comprised of a major fraction of Hb E with Hb F proportion less than 10%, without Hb A. DNA methods to confirm their genotype of Hb E homozygote and to detect other β-thalassemia mutations [5, 6], together with α-thalassemia (Southeast Asian and Thai deletions) and α-thalassemia (3.7and 4.2-kb deletions) determinants [7], were performed in all samples with Hb E homozygote phenotype. The study was approved by the institutional ethical committee. Of the 6023 couples determined by HPLC, there were 792 subjects with a phenotype of Hb E homozygote identified. Among these, 464 couples met our requirement, including 25 with double diagnoses of Hb E homozygote. The mean (± SD) Hb E and Hb F proportions in 489 Hb E homozygotes were 77.87 ± 5.27 and 3.54 ± 1.82%, respectively. After performing genotypic diagnosis, five (1.0%) Hb E/βthalassemia subjects were identified (Fig. 1). All five samples had co-inherited either α-thalassemia or αthalassemia allele. Furthermore, all five cases had a spouse who had inherited Hb E, meaning they were atr isk couples for Hb E/β thalassemia near ly misdiagnosed (Table 1). * Peerapon Wong [email protected]