Pitfalls in the Diagnosis of ß-Thalassemia Intermedia.

ABSTRACT

We present case histories of three patients who had ß-thalassemia (ß-thal) trait with 'unusual severity' managed as ß-thal intermedia (ß-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 ß-thal mutation and disease severity that did not fit in with either ß-thal trait or with ß-thal major (ß-TM). As mutations of α, ß, 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 ß-TI with certainty in some patients where the genetic basis is not clear-cut.