Compound Heterozygous Hb Milledgeville With -α4.2 Thalassemia-A Rare and First Reported Cause of Primary Erythrocytosis in an Indian Family.

Abstract

Recent review collated 22 rare and novel alpha globin gene variants amongst the Indian population published in the literature in the last 52 years. We report another rare high-oxygen affinity alpha-globin variant hemoglobinopathy in a compound heterozygous state with α⁺ thalassemia. The patient, a 42-year-old male, came for evaluation of JAK2 p.V617F negative erythrocytosis requiring multiple phlebotomies in the last 4-5 years. On laboratory investigations for high-oxygen affinity hemoglobinopathy, he was found to have an unknown peak eluting as a left shoulder hump of the Adult hemoglobin (HbA0) in Cation exchange High-Performance Liquid Chromatography (CE-Hb-HPLC). His family study revealed the variant hemoglobinopathy coexisting with a single alpha-globin deletion in the mother, sibling, and two children. Next-generation sequencing (NGS), Gap Polymerase chain reaction (GAP-PCR), and multiplex ligation probe amplification (MLPA) on the extracted DNA of the index case showed compound heterozygous state for Hb Milledgeville and -α^4.2 thalassemia. This is the first report of a rare high-oxygen-affinity alpha hemoglobin variant Hb Milledgeville from India.