title: Clinical to Molecular Screening Paradigm for β-Thalassemia Carriers.
abstract: β-Thalassemia (β-thal) represents a major health problem worldwide and particularly in Egypt. Its prevention, compared to treatment, is cost-effective, possible and practical. In this study we evaluate a proposed paradigm for detection of the β-thal carrier state. The present study included 1627 children and adolescents of both sexes, presenting as outpatients to clinics of Ain-Shams University Hospitals, Cairo, Egypt, from November 1 2009 to June 30 2010. In the first phase, after performing a complete blood count (CBC), 280 microcytic hypochromic patients were selected. These cases were further analyzed by iron profile and high performance liquid chromatography (HPLC); in the second phase, hybridization detected 22 common β-globin mutations in 74.0% of the suspected cases. Thus, by HPLC, the Hb A2 level of >3.5% provided 100.0% sensitivity, 70.0% specificity, 75.0% positive predictive value (PPV), 100.0% negative predictive value (NPV) and accuracy of 70.0% to identify β-thal trait and at a cut-off of 4.0%, it provided 97.4% sensitivity, 72.7% specificity, 92.6% PPV, 88.8% NPV and a diagnostic accuracy of 92%. High performance liquid chromatography is a reliable and cost effective primary screening tool for β-thal trait at a Hb A2 level of ≥4.0%, while molecular testing is mandatory only for selected cases with borderline Hb A2 values between 3.5 and 4.0%.
authors.affiliation: Clinical and Chemical Pathology Department, Ain Shams University , Cairo , Egypt.
authors.forename: Ibrahim Y
authors.initials: IY
authors.lastname: Abdel-Messih
authors.forename: Soha R
authors.initials: SR
authors.lastname: Youssef
authors.forename: Galila M
authors.initials: GM
authors.lastname: Mokhtar
authors.forename: Mahira I
authors.initials: MI
authors.lastname: Elmogy
authors.forename: Hanan M
authors.initials: HM
authors.lastname: Mahmoud
authors.forename: Mariz
authors.initials: M
authors.lastname: Ayoub
authors.forename: Shaimaa A
authors.initials: SA
authors.lastname: Pessar
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007501:Iron / Q000097:blood / Q000378:metabolism; D008297:Male; D008403:Mass Screening; D009154:Mutation; D010641:Phenotype; D015995:Prevalence; D012680:Sensitivity and Specificity; D055815:Young Adult; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*
chemical_list: D055544:beta-Globins; D007501:Iron
keywords: carrier screening; clinical screening; molecular screening; β-Thalassemia (β-thal)