The β-globin genotype E121Q/W15X (cd121GAA→CAA/cd15TGG→TGA) underlines Hb D/β-(0) thalassaemia marked by domination of haemoglobin D

Abstract.

Among 13,525 haemoglobin analyses performed in our laboratory we detected 21 cases of haemoglobin D (Hb D) disease. Investigation of a family affected with this abnormal haemoglobin revealed two cases of Hb D/β-(0) thalassaemia for the first time among Saudi Arabs. The two patients were diagnosed as having chronic haemolytic anaemia of moderate severity on the basis of the haemoglobin level, haematocrit, mean corpuscular haemoglobin, mean corpuscular volume, reticulocyte count, red blood cell count microscopy, elevated serum conjugated and non-conjugated bilirubin, increased serum lactic dehydrogenase, and the occasional need for blood transfusions. Genetic analysis enabled the detection of compound heterozygosity for the missense E121Q (codon 121 GAA→CAA) and stop W15X (codon 15 TGG→TGA) mutations as causative of the clinical phenotype of Hb D-LosAngeles (Punjab)/β-(0) thalassaemia. The disease manifested as domination of Hb D and moderate haemolytic anaemia. The co-inheritance of β-(0) thalassaemia seems to be responsible for conferring the deleterious effect on the presentation of Hb D disease in these patients. The present result emphasizes the significance of molecular testing in resolving certain diagnostic ambiguities in haematology as in cases of heterozygous Hb D in association with β-(0) thalassaemia which, by haemoglobin electrophoresis, may be misdiagnosed as Hb D homozygosity.