The Problem of Borderline Hemoglobin A2 Levels in the Screening for β-Thalassemia Carriers in Sardinia

Abstract

Background: The increase in HbA2 is the most important parameter for the identification of thalassemia carriers. However, in routine screening for hemoglobinopathies, some cases are difficult to classify because the level of HbA2 is not typically elevated. In this work, we report the results of a molecular investigation on a cohort of subjects with borderline HbA2. Methods: All subjects with a β-thalassemia carrier partner and a borderline percentage level of HbA2 were investigated for the presence of a pathological mutation in the β-globin gene. All negative subjects were screened for both the KLF1 mutation and the presence of ααα/ or αααα/ alleles. The subjects with reduced MCV and/or MCH were also screened for deletional and nondeletional α-globin gene defects. Results: Various β-globin mutations and KLF1 gene defects are the most common genetic determinants responsible for this phenotype in our population. Conclusion: KLF1 mutations are important in a screening program for hemoglobinopathies. An increase in HbF in association with borderline HbA2 levels is a useful but not exclusive marker that suggests the investigation of this gene. On the basis of our findings, we are able to suggest the molecular procedure to use in a population characterized by a high prevalence of thalassemia carriers.

Shine & Lal index as a predictor for early detection of β-thalassemia carriers in a limited resource area in Bandung, Indonesia

“…The increase in HbA2 becomes an important parameter for thalassemia carrier identification. However, samples with low SLI and normal or borderline HbA2 levels may suggest an IDA or possible α-thalassemia carrier with deletional or non-deletional α-globin gene defects, and this needs to be further analysed by molecular analysis [17]. The machine used in our study showed a high peak of HbE, which is clearly separated from HbA2 (Fig.…”

Red blood cells free α‐haemoglobin pool: a biomarker to monitor the β‐thalassemia intermedia variability. The ALPHAPOOL study

“…However, a few b-thal heterozygotes fail to manifest these classical haematological features and are termed as silent carriers having normal or borderline HbA 2 levels (Paglietti et al, 2016). In b-thal and a-thal, a microcytosis is observed, and the a-Hb pool parameter fully discriminates afrom b-thalassaemia.…”

“…Classical b-thal carriers have typically reduced red cell indices (MCV < 80 fl, MCH < 27 pg) with high RBCs, contrasting with the slightly lowered Hb levels and elevated HbA 2 (4-8%) and, often, Hb F levels. However, a few b-thal heterozygotes fail to manifest these classical haematological features and are termed as silent carriers having normal or borderline HbA 2 levels (Paglietti et al, 2016). a-thal carriers can also escape diagnostic hypothesis, having a normal MCV or being confused with iron deficiency.…”

The phenotypic and molecular diversity of hemoglobinopathies in India: A review of 15 years at a referral center

“…Thus delta genotyping is important particularly in couples where one of the partners is a classical β thalassemia carrier and the other has normal/borderline HbA 2 levels and they have come for testing during an ongoing pregnancy. In Sardinia, individuals with borderline HbA 2 levels are also screened for KLF1 gene mutations and α gene triplication …”

“…In Sardinia, individuals with borderline HbA 2 levels are also screened for KLF1 gene mutations and α gene triplication. 42 Deletional α thalassemia is common in India having an average prevalence of 13%. The commonest defect is the 3.7 kb deletion.…”