β-thalassemia caused by compound heterozygous mutations and cured by bone marrow transplantation: A case report

In the present study, a rare familial case of severe thalassemia with compound spontaneous mutations is reported. A 2.5-year-old boy, who suffered from severe anemia with yellowish skin, enlarged liver and spleen, was provided with a blood transfusion every 20 days to maintain hemoglobin levels between 90 and 100 g/l. Sanger sequencing combined with reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Gap-PCR revealed that the proband was a carrier of 4 compound heterozygous mutations: Hemoglobin subunit β (HBB):IVS-II-654(C>T)β(+); Southeast Asian-type-hereditary persistence of fetal hemoglobin (SEA-HPFH); HBB:c316-148G>T; hemoglobin subunit α2 (HBA2):c.46G>A. The father of the proband was identified as a carrier of the heterozygous SEA-HPFH mutation, the mother was a carrier of compound heterozygous mutations of HBB:IVS-II-654(C>T) and HBA2:c.46G>A, and the elder sister was heterozygous for HBB:IVS-II-654(C>T)β(+). Based on these genetic results, it was determined that the proband had both of heavy β-thalassemia and α-thalassemia. Upon human leukocyte antigen matching, bone marrow transplantation (BMT) was successfully performed on the proband by selecting his HLA-compatible sister as a donor. Following treatment, the proband was revealed to only carry the IVS-II-654(C>T)β(+) heterozygous mutation, and further regular blood transfusions have been avoided; BMT results remained normal at six months follow-up.