Five Rare β Globin Chain Hemoglobin Variants in India.

Area of Science:

• Hematology
• Genetics
• Molecular Biology

Background:

• Hemoglobinopathies, including thalassemias and structural hemoglobin (Hb) variants, are prevalent monogenic inherited disorders in India.
• High-performance liquid chromatography (HPLC) is a primary tool for screening and diagnosing these conditions.

Observation:

• Five rare beta-chain Hb variants (Hb British Columbia, Hb Saint Louis, Hb G Coushatta, Hb Pyrgos, and Hb Agenogi) were identified in the Indian population.
• These variants exhibited distinct elution patterns on HPLC, with some overlapping with common Hb variants (HbA2, Hb C windows).
• One case with Hb Saint Louis presented with anemia and hepatosplenomegaly, while the other four variants were asymptomatic.

Findings:

• HPLC analysis revealed specific elution profiles for each rare variant, necessitating complementary diagnostic methods.
• DNA sequencing confirmed the identity of all five rare Hb variants.
• Hb Saint Louis and Hb G Coushatta eluted in the HbA2 window; Hb British Columbia and Hb Agenogi in the Hb C window; and Hb Pyrgos in an unknown window.

Implications:

• Accurate identification of rare Hb variants is essential to avoid misdiagnosis, particularly when they mimic common variants on HPLC.
• Some rare variants, like Hb G Coushatta, can interfere with HbA1c estimations, impacting diabetes management.
• The findings underscore the importance of employing multiple diagnostic techniques for comprehensive hemoglobinopathy screening.