Hb H disease with various β hemoglobinopathies: molecular, hematological and diagnostic aspects

Abstract

We report the molecular, hematological and diagnostic features of three Thai patients with Hb H (β4) disease in combination with different β hemoglobinopathies. The first case was a boy with a hitherto undescribed condition of Hb H-Hb Tak (HBB:c.441_442insAC) syndrome. The second case was an adult male with the Hb H-Hb Hope (HBB:c.410G>A) disease. The last case was a male patient with a combination of Hb H-Hb Constant Spring (Hb CS) (HBA2:c.427T>C) and a high Hbs A(2)/F β(0)-thalassemia (β-thal) trait (the 3.4 kb deletion). In all cases, no Hb H was detected and Hb H inclusion was absent, accurate diagnosis could be obtained after DNA analysis. All of them had mild hypochromic microcytic anemia with hemoglobin (Hb) values ranging from 8.8-10.4 g/dL, PCV 0.31-0.36 L/L and MCV 57.6-66.9 fL and none had ever received a blood transfusion. The levels of Hb Tak (7.8%) and Hb Hope (21.6%), respectively, observed in the first two cases were relatively lower than values found in heterozygotes for these two variants. In the last case, the level of Hb A(2) (4.8%) was within the diagnostic range for a β-thal trait. The Hb F level was not elevated but a small amount of Hb Bart's was observed. Hematological findings and diagnostics using combined Hb and polymerase chain reaction (PCR) analyses are presented and compared with those of the other Thai patients with Hb H-β(0)-thal, Hb H-Hb CS-Hb J-Bangkok (HBB:c.170G>A) and Hb H-Hb CS-Hb Pyrgos (HBB:c.251G>A) previously observed in our series.