Discrepant clinical haematology features in siblings of Pakistani origin with β-thalassaemia

Abstract

Background:
An eight year old boy was referred with anaemia and splenomegaly. Physical examination revealed short stature, thalassaemic facies, pallor and splenomegaly.

Results:
The FBC showed a hypochromic, microcytic anaemia. Serum ferritin was normal. Haemoglobin electrophoresis revealed 56% HbF, 2.3% HbA2 and 41.7% HbA.

Using polymerase chain reaction (PCR) and deoxyribonucleic acid (DNA) sequencing, two different β-thalassaemia mutations were identified in the parents. Both parents thus had a β-thalassaemia trait whilst 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 α+-thalassaemia and hereditary persistence of foetal haemoglobin (HPFH) deletions as well. This showed that the daughter had inherited a single α gene deletion from her mother which the son had not. Studies for HPFH mutations revealed that all four family members had one γ point mutation.

Conclusion:
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-deletion HPFH gene which her brother did not.