Severe Drug-Induced Hemolysis in a Patient with Compound Heterozygosity for Hb Peterborough (HBB: c.334G>T) and Hb Lepore-Boston-Washington (NG_000007.3: g.63632_71046del)

Abstract

Unstable hemoglobins (Hbs) are often overlooked in the differential diagnoses of drug-induced hemolysis. Hb Peterborough [β111(G13)Val→Phe; HBB: c.334G>T] is a rare unstable Hb variant, predominantly found in individuals of Italian descent, due to a structural defect involving a single amino acid substitution (phenylalanine for valine at position 111 of the β-globin chain). Unstable Hb variants are often inherited in the heterozygous state with Hb A (α2β2) and rarely in compound heterozygosity with other Hb variants. The presence of another variant Hb often alters the phenotype, occasionally resulting in more severe disease. Using a combination of molecular techniques; multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing, we identified a compound heterozygosity for Hb Peterborough and Hb Lepore-Boston-Washington (Hb LBW) [δ87, β116; NG_000007.3: g.63632_71046del] in a middle-aged gentleman with a history of chronic microcytic anemia and splenomegaly, presenting with severe drug-induced hemolysis, which was managed conservatively. The clinical history and presentation reflect the dual pathology due to the presence of two variant Hbs and their associated phenotypes. In this article, we discuss the phenotype resulting from the interaction of Hb Peterborough and Hb LBW and emphasize the importance of molecular testing in the diagnosis of rare Hb variants.

Keywords:

• Hemoglobinopathy
• Hb Lepore-Boston-Washington (Hb LBW)
• Hb Peterborough
• hemolysis
• unstable hemoglobin (Hb)

Acknowledgments

The authors thank the patient for giving consent for the publication of this case. The following contributions were made by the authors: C. Agbuduwe performed the literature review and wrote the first draft of the paper; N. Asba performed the initial laboratory assessments of the patient’s samples; M. Rugless and M. Proven performed the molecular analyses and contributed to the description of the laboratory methods; M. Sivakumaran was the lead clinician for this case and supervising author. All authors reviewed and approved the final draft of the paper.

Disclosure statement

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

Additional information

Funding

The publication of this article was supported by a Peterborough City Hospital Research Fund. C. Agbuduwe’s Academic Clinical Fellowship is funded by the National Institute for Health Research.