A rare case of Hb H disease caused by compound heterozygous for α thalasemia and Hb Quong Sze in Chinese Indonesian proband: A case report

Background: Hemoglobin H (HbH) disease is alpha thalassemia characterized by inactivation of three of four alpha-globin genes due to deletions with or without non-deletional alpha-thalassemia. Hb Quong Sze (Hb QS) is a very rare non-deletional alpha-thalassemia in Indonesia caused by a CTG(Leu)>CCG(Pro) nucleotide substitution at codon 125 of alpha(2) globin gene generating highly unstable hemoglobin. Compound heterozygosity for Hb QS and Southeast Asian double alpha-globin gene deletion (--(SEA)) result in accumulation of b-globin tetramers, causing hemolytic anemia. Case Report: A 49 years old Chinese Indonesian female was assessed for thalassemia screening. The phenotype of the proband was normal and only mild anemia was noticeable. She experienced blood transfusion five years ago due to a sudden fall of hemoglobin level after malarial infection. Complete blood count found hemoglobin 8.3 g/dL, Mean Corpuscular Volume (MCV) 65.7 fl and Mean Corpuscular Hemoglobin (MCH) 17.1 pg. HbH disease suggested by abundant Hb H inclusion bodies in the red blood cells. Microcapillary hemoglobin electrophoresis result showed HbH 31.8 %, Hb Bart 0.4%, HbA 67.3% and HbA(2) 0.5%. Molecular studies were carried out using multiplex polymerase chain reaction (PCR) method, and the common a(0)-thalassemia(--SEA) was detected in one allele. Direct sequencing analysis of the alpha(1) and alpha(2) globin genes revealed Hb QS in the other allele. Conclusion: Non-deletional Hb H disease due to compound heterozygous of Hb QS with Southeast Asian double alpha-globin gene deletion (--(SEA)) has a very low incidence in Indonesia. An advanced molecular analysis should be performed to determine this rare mutation.