# Analysis of Common Alpha-Globin Gene Abnormalities and Their Effects as Genetic Modifiers in Thai Children With β-Globin Gene Abnormalities

## TL;DR

This study examines how α-globin gene mutations affect the severity of β-thalassemia in Thai children, showing that these mutations can modify clinical outcomes and hematological parameters.

## Contribution

The study provides new insights into the role of α-globin gene mutations as genetic modifiers in pediatric β-thalassemia patients in Thailand.

## Key findings

- Coinheritance of α-globin mutations was less frequent in β-thalassemia diseases than in β-thalassemia traits.
- Single α-globin deletions or Hb CS mutations were linked with lower Hb E, MCV, and MCH in β-thalassemia/Hb E patients.
- Hematological parameters can help identify α-globin mutations, improving diagnosis of complex thalassemia syndromes.

## Abstract

Beta-thalassemia exhibits a broad phenotypic range influenced by the severity of HBB mutation and various genetic modifiers. One of the most essential modifiers is the coinheritance of α-globin gene mutation. Nevertheless, the understanding of these α-globin variations' impact on beta-thalassemia is lacking among pediatric patients. This study investigated the impact of common α-globin gene mutations on clinical phenotype and hematological parameters in 122 Thai children with either β-thalassemia diseases or carriers recruited from Phramongkutklao Hospital, a major thalassemia center. Clinical characteristics, transfusion history, and hematological parameters were recorded, with molecular testing for common α-globin deletions and Hb CS mutations. The cohort included 8 homozygous β-thalassemia, 55 β-thalassemia/Hb E, 18 homozygous Hb E, 26 heterozygous Hb E, and 15 heterozygous β-thalassemia children. Coinheritance of α-globin mutations was less frequent in β-thalassemia diseases (6 of 63) than in β-thalassemia traits (25 of 59) (p < 0.001), indicating a potential modifier effect that reduces severity. Among β-thalassemia/Hb E patients, single α-globin deletions or Hb CS mutations were linked with lower Hb E, MCV, and MCH. Similarly, in both β-thalassemia and Hb E traits with α-globin gene mutation had significantly lower MCV, MCH and Hb E levels (only in the Hb E trait) and elevated RDW. Moreover, lower hematocrit and hemoglobin in these carriers were noted in cases coinherited with deletional Hb H disease initially undiagnosed by Hb typing. In conclusion, the diagnostic value of hematological parameters and Hb typing in identifying common α-globin mutations in pediatric β-thalassemia patients were highlighted. Hematological parameters are vital indicators that may prompt genetic screening to confirm α-globin abnormalities, supporting improved diagnosis and management of complex αβ-thalassemia syndromes.