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

Abstract

Background: Hemoglobin H (HbH) disease is alpha thalassemia characterized by inactivation of three of four α-globin genes due to deletions with or without non-deletional α-thalassemia. Hb Quong Sze (Hb QS) is a very rare non-deletional α-thalassemia in Indonesia caused by a CTGLeu>CCGPronucleotide substitution at codon 125 of α2 globin gene generating highly unstable hemoglobin. Compound heterozygosity for Hb QS and Southeast Asian double α-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 HbA2 0.5%. Molecular studies were carried out using multiplex polymerase chain reaction (PCR) method, and the common a0-thalassemia(--SEA) was detected in one allele. Direct sequencing analysis of the α1 and α2 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 α-globin gene deletion (--SEA) has a very low incidence in Indonesia. An advanced molecular analysis should be performed to determine this rare mutation.

Molecular and Haematological Characteristics of alpha-Thalassemia Deletions in Yogyakarta Special Region, Indonesia

“…In Indonesia, alpha-Thalassemia cases has been widely reported (4)(5)(6)(7). However, a study that specifically discussed about its molecular characteristics such as breakpoint site of deletions is still limited.…”

Clinical and Haematological Parameters of Commonly Reported Non-deletional α-thalassaemia Mutations in Southeast Asia: A Review

“…Although it has been reported in Thailand and China (20), Hb QS is still rare, with less than 1 % only of the Chinese population in Malaysia bearing this mutation (30).…”

“…The clinical severity depends on the mutation, whether it fully or partially reduces the production of remaining α-globin chains (43). Usually, non-deletional mutations will lead to Hb variants without any serious clinical significance; hence, if the mutations occurred in an important amino acid residue, it would cause a reduction in the production of α-globin chains that results in haemolytic anaemia (30).…”

“…However, the presence of compound heterozygous Hb variant of non-deletional and other types of α-thalassaemia mutation is more unstable and produces severe clinical presentations, such as haemoglobin H (HbH) disease (30). Non-functionality of HBA2 resulting from deletions will be compensated with increased expression of HBA1.…”

“…Babies born with this condition would also require regular blood transfusions (59). However, the Hb QS is a highly unstable Hb, so it is undetectable in routine electrophoresis and HPLC methods (30).…”