Compound Heterozygosity of Hemoglobin Jax (HBA2:c.44G>C) and Hemoglobin Constant Spring (HBA2:c.427T>C) Resulting in Microcytic Anemia in a Thai Woman

Objective:Rare disease Background:Thalassemia and hemoglobin (Hb) variants are the most common hereditary red blood cell disorders worldwide.Alpha-thalassemia and alpha-globin variants are caused by mutations of the alpha-globin genes (HBA2 and HBA1), resulting in impaired alpha-globin production and structurally abnormal globin, respectively.Clinical severity of alpha-thalassemia correlates with the number of affected alpha-globin genes, yielding a spectrum of clinical manifestations from mild to severe anemia.Routine diagnosis involves Hb analysis and PCR-based methods, yet identifying rare variants necessitates comprehensive clinical and hematologic laboratory data.The knowledge of phenotype and genotype correlation is useful for genetic counseling and treatment planning. Case Report:A 59-year-old Thai woman presented with chronic anemia.Her baseline Hb level ranged between 8.0 and 9.0 g/dL, with no history of transfusion.Physical examination showed mild pallor, without enlarged liver and spleen.Laboratory investigations showed microcytic, hypochromic anemia and abnormal Hb peak by Hb analysis (retention time 4.58 min by HPLC method).Common alpha-globin gene deletions, including the Southeast-Asian/Thai 3.7 kb and 4.2 kb deletions were tested using gap-PCR, with none of these deletions detected.Direct DNA sequencing revealed a compound heterozygosity of Hb Jax (HBA2: c.44G>C) and Hb Constant Spring (HBA2: c.427T>C). Conclusions:Compound heterozygosity of Hb Jax and Hb Constant Spring results in microcytic anemia.Hb Jax can be identified by Hb analysis, and diagnosis can be confirmed by direct DNA sequencing method.Coinheritance of Hb Jax and alpha-globin variants should be considered in cases with microcytic anemia and a specific Hb peak seen in Hb chromatogram.