Time-of-flight mass spectrometry in the diagnosis of haemoglobin Kenya

Abstract

Haemoglobin (Hb) variants are routinely detected by electrophoresis and high performance liquid chromatography (HPLC) in clinical laboratories. However, further molecular testing is often required to achieve a diagnosis. For rare variants molecular analysis may involve investigation of both the α- and β-globin gene clusters, as well as multiple techniques to detect point mutations and gene duplications or deletions. Time-of-flight (TOF) mass spectrometry is used as a secondary test in our laboratory to guide molecular analyses, saving both time and money. We present a case of Hb Kenya, a rare variant not typically seen in our patient population. Hb Kenya is associated with hereditary persistence of fetal haemoglobin (HPFH) and is the product of a γβ fusion gene arising from abnormal crossing over during meiosis. This variant is not easily diagnosed by routine haematology or genetic methods and may be confused with other disorders. TOF mass spectrometry was used to identify the variant mass, enabling appropriate molecular testing to be designed for confirmation of the diagnosis. This case highlights the utility of TOF mass spectrometry for haemoglobinopathy and thalassaemia investigations.