Role of iron deficiency anemia in the propagation of beta thalassemia gene Usman, M., Moinuddin, M., Ahmed, S.A. (2011) Korean J Hematol 46: Microcytic hypochromic normal rbc

Background Normal hemoglobin is HbA,  2  2, carries oxygen – Other forms are HbA 2  2  2 ; HbF  2  2 (normally gone at birth)  -thalassemia is autosomal recessive defect in production of  -chain of hemoglobin Thalassemia major is homozygote for mutant  -chain Thalassemia minor is heterozygote carrier (trait, BTT) Diagnosis shows microcytic hypochromic anemia, nucleated rbc, decreased HbA, increased HbA 2 and HbF; Molecular diagnosis (PCR) can test for common mutations

Background Severe disease, shortened life expectancy One of most common genetic disorders in Pakistan Treatment of thalassemia requires many transfusions Complications from iron overload, chelation therapy Preventive program is based on identification of carriers: elevation of HbA 2 >3.5% However, iron deficiency anemia (IDA) decreases amount of hemoglobin -> HbA 2 seems normal in person with BTT and IDA.

Experimental plan Test large number of women for BTT and IDA – Blood tests, hemoglobin electrophoresis, – Molecular diagnosis for common mutations (PCR) Determine whether any BTT and IDA patients Treat the IDA patients with oral iron, and see if HbA 2 levels change.

Results 34 of 200 women were anemic Hb electrophoresis showed 16 BTT (inc HbA 2 ) Molecular diagnosis confirmed these 16 also 8 more - those 8 had BTT and IDA 10 just had IDA (serum ferritin levels)

PCR identifies common mutations in HbB gene

Molecular spectrum of mutations identified Table 1

Iron treatment restores HbA 2 levels in patients with IDA; also reveals BTT in the BTT-IDA patient Table 2

Conclusions  -thalassemia is a serious disease, autosomal recessive, most common genetic disorder in Pakistan Preventive efforts require identification of carriers (BTT) – As increased level of HbA 2 because less  chain Iron deficiency anemia (IDA) results in lower Hb overall, and also HbA 2 IDA in patient with BTT can mask the carrier state. Any patient suspected of BTT should be tested for iron deficiency, which is corrected by iron treatment