An 8-year-old boy was referred with anaemia and splenomegaly. Physical examination revealed short stature, thalassaemic facies, pallor and splenomegaly. The full blood count showed a hypochromic, microcytic anaemia. The serum ferritin level was normal. Haemoglobin electrophoresis revealed 56% HbF, 2.3% HbA2 and 41.7% HbA. The boy's younger sister was subsequently found to have a mild hypochromic, microcytic anaemia with a marked increase in HbF level.
Using the polymerase chain reaction (PCR) and deoxyribonucleic acid (DNA) sequencing, two different β-thalassaemia mutations were identified in the parents. Both parents therefore had a β-thalassaemia trait, while both children were compound heterozygotes.
The propositus had become transfusion dependent while his sister had managed to maintain her Hb above 8.5 g/dl. The family was studied for β+-thalassaemia and hereditary persistence of fetal haemoglobin (HPFH) deletions. This showed that the daughter had inherited a single β-gene deletion from her mother while the son had not. Studies for HPFH mutations revealed that all four family members had one β-point mutation.
The presence of HPFH in this family cannot be considered to have any effect on the thalassaemia major phenotype as neither of these β-mutations are known to be associated with any HbF induction. It is also possible that the daughter inherited a non-deletional HPFH gene which her brother did not.