Pitfalls in the Diagnosis of β-Thalassemia Intermedia

Abstract

We present case histories of three patients who had β-thalassemia (β-thal) trait with ‘unusual severity’ managed as β-thal intermedia (β-TI) where the basis of disease severity could not be explained with routine hematological and genetic investigations. The clinical diagnosis of ‘thalassemia intermedia’ was justifiable as they had a β-thal mutation and disease severity that did not fit in with either β-thal trait or with β-thal major (β-TM). As mutations of α, β, and γ genes could not explain the unusual severity of the disease, further analysis with next-generation sequencing (NGS) for red cell diseases was carried out, which led to the diagnosis of coexisting membranopathies. This case series highlights the inherent difficulty in the diagnosis of β-TI with certainty in some patients where the genetic basis is not clear-cut.

Keywords:

• β-Thalassemia intermedia (β-TI)
• phenotypic diversity
• red cell membranopathy

Acknowledgments

This article is dedicated to the memory of the late Professor Sir David J. Weatherall, who played a pivotal role in this study by providing funding and invaluable insight and for contributions to the study design.

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

This study was supported in part by National Research Council, Sri Lanka Research Grant No. NRC 09/13 and University Grant Commission, Sri Lanka Research Grant No. UGC/ICD/CRF/2009/29/1.