Clinical analysis of abnormal hemoglobin detection results in northern Guangxi, China

To characterize the epidemiological profile, variant spectrum, and clinical phenotypes of abnormal hemoglobins in the northern Guangxi region of China, and to establish and validate a tiered diagnostic strategy combining capillary electrophoresis with multi-platform molecular techniques, thereby providing evidence for regional prevention and control of hemoglobinopathies.

A retrospective study was conducted. A total of 3890 individuals of reproductive age who visited Guilin People's Hospital between March 2022 and March 2025 underwent initial screening by capillary electrophoresis. Samples confirmed to carry true hemoglobin variants were subjected to genotyping using reverse dot blot hybridization, Sanger sequencing, and third-generation sequencing (TGS). The electrophoretic characteristics, hematological parameters, and genotype-phenotype correlations of different globin variants were analyzed.

The overall detection rate of abnormal hemoglobins was 1.13% (44/3890), encompassing three α-globin and six β-globin variants. HbE was the predominant variant (0.46%), followed by Hb New York. Rare variants, including HbO-Arab and Hb Barcelona, were also identified. The compound variant -α^4.2α^Q-Thailand/--^SEA manifested as a typical HbH disease phenotype. Double heterozygotes for HbE and β-thalassemia frequently presented with moderate or severe thalassemia requiring long-term clinical intervention. Most simple heterozygotes of β-globin variants exhibited essentially normal hematological parameters. Due to their unaltered net molecular charge, electrophoretically silent variants such as Hb Hekinan II were challenging to detect by conventional capillary electrophoresis, posing a risk of missed diagnosis.

Abnormal hemoglobins in the northern Guangxi region of China display a distinct variant spectrum dominated by HbE. Capillary electrophoresis is suitable for large-scale population screening, and its integration with multi-tiered molecular testing compensates for the limitations of electrophoretic methods, enabling precise identification of rare and silent variants. Implementing genetic counseling and prenatal diagnosis for high-risk populations is a crucial measure to reduce the incidence of severe hemoglobinopathies.