การศึกษาผลลัพธ์จากการเปลี่ยนเกณฑ์การวินิจฉัยพาหะของ beta-thalassemia โดยใช้ระดับ hemoglobin A2 มากกว่าร้อยละ 3.5 ในระบบการควบคุมโรค betathalassemia ในเขตภาคเหนือตอนล่าง
Keywords:
beta-thalassemia, hemoglobin A2, at-risk coupleAbstract
Introduction: In Thailand, mass screening of beta-thalassemia carrier state for prenatal control by determining the hemoglobin (Hb) A2 fraction is a mainstay of the diagnostic method. Currently, the cut-off value of 4.0% or greater has been replaced with the fraction of more than 3.5% by the Department of Medical Sciences, Ministry of Public Health.
Objective: The study aimed to detect beta-thalassemia heterozygotes in samples with Hb A2 levels ranging from 3.6 - 3.9% and to study the impact of the new cut-off value on numbers of carriers and at-risk couples identified.
Method: Hb analysis records of couples who had been investigate for beta-thalassemia risk were collected at the Thalassemia Research Unit, Naresuan University Hospital between October 2014 and December 2018. Real time-PCR with high resolution melting analysis and DNA sequencing were performed to detect betaglobin mutations in blood specimens with Hb A2 values between 3.6 and 3.9%. All new beta-thalassemia carriers identified together with results of their spouses were re-evaluated for new at-risk couples. Numbers of new carriers and at-risk couples identified were determined with numbers derived using the former criterion.
Results: Among 7,110 couples, 41 samples with Hb A2 fraction between 3.6 and 3.9% were detected and diagnosed with new beta-thalassemia carriers. From the 41 samples, 7 beta-thalassemia alleles were identified (17.1%). In all, 2 beta0-thalassemia [IVS-1 nucleotides (nt) 1 (G>T), codon 41/42 (-TTCT)] and 5 beta+-thalassemia heterozygotes [nt-31 (A>G), nt -28 (A>G), codon 126 (GTG>GGG)] were identified. Adjusting the cut-off values added 26 (9.9%) more phenotypic and 4 (1.5%) more genetically proven at-risk couples.
Conclusion: The increment of false-positive numbers of at-risk couples resulted from the new cut-off level of Hb A2 seemed negligible compared with the total numbers of at-risk couples identified. However, some false-positive couples may obtain unnecessary obstetric procedures for prenatal diagnosis.
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References
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