Hemoglobin A2 (HbA2) has a measure of unreliability in diagnosing β-thalassemia trait (β-TT). (4th May 2018)

• Record Type: Journal Article
• Authors: Al-Amodi, Amani M.; Ghanem, Neda Z.; Aldakeel, Sumayh A.; Ibrahim Al Asoom, Lubna; Rafique Ahmed, Nazish; Almandil, Noor B.; Naserullah, Zaki A.; Al-Jarrash, Sana; Shakil Akhtar, Mohammed; AbdulAzeez, Sayed; Al-Ali, Amein K.; Borgio, J. Francis
• Is Part Of: Current medical research and opinion. Volume 34:Number 5(2018)
• Page Start: 945
• Page End: 951
• Publication Date: 2018-05-04
• Subjects: β-Thalassemia carriers -- Pre-marital screening -- Molecular diagnosis -- Globin genes -- Hemoglobin A2 (HbA2) -- Borderline HbA2 -- β-Thalassemia trait -- Mutation; Clinical medicine -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1080/03007995.2018.1435520
• Languages: English
• ISSNs: 0300-7995

Abstract

Abstract: Introduction: Detection of β-thalassemia trait or carriers (β-TT) depends significantly on an increase in Hemoglobin A2 (HbA2 ) levels, which is found at low levels (<3%) in normal healthy individuals and elevated levels (≥3.5%) in β-TT individuals. The study was designed to evaluate the reliability of the diagnostic parameter HbA2 in the differentiation of β-TT and non-β-TT in Saudis. Methods: The widely used high performance liquid chromatography (Variant II Bio-Rad) was used to measure HbA2 levels in blood. Sanger sequencing was used to screen the variation in globin genes ( HBB, HBD, HBA1, and HBA2 ). All the study subjects were divided into βTT and non-βTT (wild) categories based on the presence or absence of HBB variations and further sub-divided into false positive, true positive, false negative, and true negative, based on HbA2 values. Results: Out of 288 samples, 96 had HBB gene mutations. Of the 96 β-TT samples, sickle cell trait (SCT) samples ( n = 58) were excluded, while the remaining (38 β-TT) were included in the detailed analysis: seven subjects with the HBB mutation had normal HbA2 (<3%), and three were borderline (3.1–3.9%). The remainder ( n = 28) had an elevated HbA2 level (>4%). Based on HbA2 analysis alone, both these groups would be incorrectly diagnosed as normal. Similarly, of the 189 non-β-TT samples, 179 had normal HbA2, eight had borderline HbA2, and two had a HbA2 level above 4%. Based on HbA2 analysis alone, borderline and >4% HbA2 individuals, negative for β-TT, can be incorrectly diagnosed as carriers. Conclusion: Given the percentage of samples falling in the HbA2 "borderline" and "normal" categories, it can be concluded that HbA2 has a measure of unreliability in the diagnosis of β-thalassemia carriers.