A Coincidental Discovery of a New Stable Variant (Hb Hachioji or HBB: c.187C>T) in a Patient with Chronic Hemolytic Anemia of Unexplained Origin

Abstract

We report a new hemoglobin (Hb) variant, Hb Hachioji (HBB: c.187C>T), which was detected in a 32-year-old male with hemolytic anemia. The proband had undergone splenectomy in his childhood after being diagnosed with hereditary spherocytosis (HS) with no clinical improvement. A recent study showed that Heinz bodies were frequently observed in his red cells, however, no abnormal band was separated by isoelectric focusing (IEF), and the isopropanol (instability) test was negative. Direct sequencing revealed that the proband was a heterozygous carrier of a novel mutation (GCT>GTT) at codon 62 of the β-globin gene, leading to an alanine to valine substitution. This variant was named Hb Hachioji. Characterization at the mRNA level by cDNA sequencing detected β^Hachioji mRNA, as well as β^A mRNA. Subsequently, study of the proband’s family indicated that his father was a carrier of this Hb variant, although unexpectedly, the father was asymptomatic and clinically healthy. Oxygen affinity measurement of total Hb showed no alteration in the P₅₀ and oxygen equilibrium curve. The presence of Hb Hachioji was confirmed by mass spectrometry (MS). Hb Hachioji comprised approximately 50.0% of the total Hb and was a stable variant. The phenotypic discrepancy between these two carriers suggests that Hb Hachioji may not be associated with the hemolytic involvement in the proband. P4.2Nippon, which is the primary cause of most cases of Japanese HS, was absent in the proband’s parents. The coexistence of glucose-6-phosphate dehydrogenase (G6PD) deficiency was ruled out. Thus, the cause of hemolytic involvement in this patient remains unclear.

Keywords:

• Abnormal hemoglobin (Hb)
• β-globin gene variant
• Hb Hachioji

View correction statement:

Correction

Acknowledgments

We thank the proband and his parents for participating in the study. The authors would like to express gratitude to Professor Emeritus Yuzo Ohba, MD, PhD, Mr. Kunimitsu Yamamoto (Yamaguchi University, Ube, Japan), and Professor Emeritus Yukio Hattori, MD, PhD (Yamaguchi Saisekai General Hospital, Yamaguchi, Japan), for their advice on the methods used and for reviewing our manuscript. We thank Professors Rosanna McMaster, RN, PhD, and Teresa Stone, RN, PhD (Yamaguchi University, Ube, Japan), for proofreading our manuscript.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.