Prevalence of Alpha-Globin Gene Deletions amongst Patients with Unexplained Microcytosis in a North-American Population.

Introduction: Increasing multi-ethnicity is likely to make α-thalassemia more prevalent in western metropolitan areas. The current prevalence of α-thalassemia in regions outside the traditional thalassemia areas with the associated risk for HbH disease and hydrops foetalis is unknown. Genetic counseling for reproductive risks due to α-globin gene mutations requires adequate and precise genotyping.

Objectives: To determine by multiplex polymerase chain reaction (m-PCR) the prevalence and genotypes of α-thalassemia among non selected, consecutive cases of unexplained microcytosis identified in a clinical hematology laboratory. To evaluate if differences or variations in erythrocytic indices are indicative of α-thalassemia.

Methods: During a period of 3 months, α-globin genotype was determined by m-PCR on all non repetitive microcytic (MCV <80fL) blood samples from adults with normal ferritin and normal hemoglobin HPLC analysis (Variant I, Bio-Rad). A previously described m-PCR analysis allowed the detection of α-globin gene deletions and specifically identified each of the following 7 deletions when present: −α^3.7, −α^4.2, −−^SEA, −−^FIL, −−^MED, −−^THAI and −α^(20.5).

Results: 516 microcytic blood samples were evaluated of which 197 had normal ferritin and Hb HPLC analysis and were submitted for m-PCR. Among 196 interpretable m-PCRs, 148 did not have α-globin gene deletion(s) (group 1) and 48 α-thalassemia cases (24,5%) were identified: 28 cases of single α-globin gene deletion (group 2) and 20 cases of 2 α-globin gene deletions (group 3). In group 3, 6 cases showed deletions in cis. Results on differences between the groups are presented in Table 1. Even though some differences were statistically different, none was clinically useful and diagnostic.

Conclusion: A significant proportion (24,5%) of cases with microcytosis not likely explained by iron deficiency, inflammation or a hemoglobinopathy are caused by α-globin gene deletion(s). This laboratory survey, despite a short period of sample collection (3 months) identified 6 carriers of a 2 gene deletion in cis that may have a severe impact on reproductive decisions and potential future utilisation of resources. These findings are likely to be reproducible in other North American cosmopolitan cities where α-thalassemia is not endemic but likely to be of increasing prevalence due to immigration. The availability, precision and reliability of diagnostic methods such as m-PCR and the increasing ethnic diversity of North-American cities point to an emerging need to develop genetic counseling programs based on the molecular diagnosis of α-thalassemia.

Erythrocytic parameters with their standard deviation in the different α-globin genotype groups