Thalassemia Phenotypes and Genotypes in Taiwan: A Retrospective Study Based on Thalassemia Screening of Young Men for Military Conscription

Abstract

Prenatal thalassemia studies from Taiwan show that one-third of fetuses with genetic abnormalities have β-thalassemia major (β-TM). However, the phenotypes and genotypes of adult thalassemia warrant further investigation. From September 2006 to April 2014, 741 male candidates drafted for military service with mean corpuscular volume (MCV) <80 fL and serum ferritin >20 µg/L were analyzed. The results showed that the detection rates of α- and β-thalassemia (α- an β-thal) were 50.20% (372/741) and 49.12% (364/741), respectively. Only five patients (0.67%) were diagnosed with both α- and β-thal. The - -(SEA)/αα mutation was found in 76.88% (286/372) of α-thal patients. Heterozygous mutations in IVS-II-654 (C > T) and codons 41/42 (-TCTT) accounted for 55.77% (203/364) of β-thal cases. The leukocyte counts for α- and β-thal were 6241.74 ± 1552.99 and 6622.87 ± 1814.41 × 10(9)/L, respectively (p = 0.007). The α-thal patients had lower red blood cell (RBC) mass (5.85 ± 0.44 × 10(12)/L vs. 6.09 ± 0.45 × 10(12)/L; p < 0.001) and higher hemoglobin (Hb) (12.82 ± 0.72 vs. 12.35 ± 0.71 g/dL; p < 0.001) than β-thal patients. Mean serum ferritin values were 169.67 and 241.36 µg/L, respectively, in α- and β-thal patients (p < 0.001), indicating more profound ineffective erythropoiesis in β-thal. Only four of the 741 patients underwent further hematological follow-up. Our study suggests that iron overload might be a potential problem in β-thal patients; therefore, regular follow-up is highly recommended.

A validation and modification of PLASMIC score by adjusting the criteria of mean corpuscular volume and international normalized ratio

“…Thalassemia is more prevalent in Mediterranean areas and parts of East Asia, including Taiwan, probably related to ethnicities/races 35,36 . The prevalence of alpha and beta‐thalassemia carrier in Taiwan was at least 3% to 4% and 1% to 2%, respectively 37‐39 . In our cohort, one patient had medical record of alpha‐thalassemia, which was likely to be a silent carrier or minor, and one had beta‐thalassemia minor.…”

“…35,36 The prevalence of alpha and betathalassemia carrier in Taiwan was at least 3% to 4% and 1% to 2%, respectively. [37][38][39] In our cohort, one patient had medical record of alpha-thalassemia, which was likely to be a silent carrier or minor, and one had beta-thalassemia minor. Regarding INR, previous studies that focused on the INR range in anticoagulant therapy implied that ethnic/racial background is likely to be a determinant.…”

Causal links of α-thalassemia indices and cardiometabolic traits and diabetes: MR study

“…62 participants with microcytic hypochromic erythrocytes and one participant with normocytic hypochromic erythrocytes had a large deletion involving the α-globin gene region: 58 individuals had an ∼20-kb deletion, 4 had an ∼30-kb deletion, and 1 had an ∼33-kb deletion ( Fig 5C–F ). Because the α 0 thalassemia -- SEA 20-kb deletion in the α-globin gene is the most common cause of α-thalassemia in the Taiwanese population ( Chen et al, 2002 ; Chao et al, 2014 ; Lee et al, 2015 ; Wang et al, 2017 ), we conducted tests to detect the presence of this deletion in 1,474 participants who had WGS data and genomic DNA available for analysis ( Fig 5G ). By performing PCR, we detected the α 0 thalassemia -- SEA 20-kb deletion in the α-globin gene in 60 participants, including 58 participants screened using BreakDancer (57 participants had an MCV of <80 fl and an MCH of <25 pg/RBC and one had an MCV of >80 fl and an MCH of <25 pg/RBC) and two participants who lacked BreakDancer data (one participant had an MCV of >80 fl and an MCH of <25 pg/RBC and another participant had an MCV of <80 fl and an MCH of >25 pg/RBC; Fig 5L ).…”

“…Finally, more than 100 genetic forms of α-thalassemia have been identified in which α 0 -thalassemia is usually the most common clinically relevant form (Giardine et al, 2014). In Taiwan, the -SEA type of the α 0 -thalassemia mutation is the most common deletion mutation, accounting for 69-91% cases; this finding indicates that the prevalence of this mutation is ~4.0-4.5% in Taiwanese individuals (Chen et al, 2002;Lee et al, 2015;Wang et al, 2017). All the three SNPs are specific to the Asian population and highly linked to the microcytic hypochromic trait, with a minor allele frequency of ~1.77-1.94%.…”

“…Microcytic anemia may be caused by genetic or nongenetic factors, and three subgroups of inherited microcytic anemia have been classified based on the causative defects: hemoglobinopathies (thalassemia) caused by defects in globin chain synthesis, defects in heme synthesis, and defects in iron availability or acquisition by erythroid precursors ( DeLoughery, 2014 ; Cappellini et al, 2020 ). Although most of the genetic causes of microcytic anemia are rare in terms of occurrence and each mutation contributes to a small proportion of patients with microcytic anemia, some mutations may be dominant in distinct ethnic populations, such as α 0 thalassemia deletion -- SEA , -- Fil , and -- THAI in the Southeast Asian region ( Chen et al, 2002 ; Iolascon et al, 2009 ; Harteveld & Higgs, 2010 ; Chao et al, 2014 ; Lee et al, 2015 ; Wang et al, 2017 ; Farashi & Harteveld, 2018 ; Mettananda & Higgs, 2018 ; Cappellini et al, 2020 ).…”