Alpha-Globin Gene Triplication in Central Thailand: Prevalence, Haematological Findings and Clinical Impact With...

We aimed to ascertain the prevalence of ααα^anti-3.7 and ααα^anti-4.2 triplications in central Thailand and to characterise the phenotypes of individuals harbouring these variants.

We performed a retrospective review of adult (≥ 18 years) samples submitted for polymerase chain reaction-based α-globin mutation analysis at Siriraj Hospital, Mahidol University, Bangkok (January 2012-December 2021). Haematological indices were compared between carriers and non-carriers of α-globin triplications, and clinical severity was assessed in those with co-inherited β-globin mutations.

Among 1559 subjects, α-globin triplication prevalence was 1.28%, with ααα^anti-4.2 (0.83%) more frequent than ααα^anti-3.7 (0.45%). Double heterozygosity for an α triplication and a β-globin mutation occurred in 0.9%. Individuals carrying ααα^anti-3.7 or ααα^anti-4.2 had lower mean haemoglobin levels (10.00 and 11.23 ± 1.85 g/dL, respectively) than those without triplication (12.35 ± 2.59 g/dL). Among heterozygous β-thalassaemia individuals, co-inheritance of ααα^anti-3.7 or ααα^anti-4.2 was associated with significantly reduced mean haemoglobin (8.38 ± 1.58 and 8.28 ± 1.15 g/dL, respectively). This contrasts with the non-triplication group (11.14 ± 1.86 g/dL). Of 14 subjects with double heterozygosity, 8 had thalassaemia intermedia and 6 had thalassaemia trait.

Although uncommon in central Thailand, α-globin triplications can exacerbate anaemia in individuals with co-inherited heterozygous β-globin mutations, supporting routine screening in symptomatic cases. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.