Final Diagnosis -- A 31-year-old female with Hb SC disease

The majority of hemoglobin variants result from changes in the amino acid sequence of either the α or non α globin chains of hemoglobin with the majority of these changes due to a single point mutation in the globin gene. Substitution, insertion, deletion or the combination of deletion with insertion of a different amino acid than that normally present result in changes to the aminoacid sequence. Over 900 hemoglobin variants have been described to date. Many hemoglobin variants have minimal clinical significance and are a fortuitous finding sometimes as the result of HbA1c analysis.

Methods for identification of hemoglobin variants are classified as either presumptive or definitive. Presumptive methods include high performance liquid chromatography (HPLC) and electrophoresis at both alkaline and acid pH. These methods are relatively straightforward to perform in the routine laboratory and can provide a reliable (but not completely definitive) identification of many of the common hemoglobin variants.

Each of the presumptive hemoglobin variant methods has limitations in hemoglobin variant identification. Definitive hemoglobin variant identification methods include DNA analysis of the globin genes and liquid chromatography/mass spectrometry (LC/MS)

REFERENCES:

1. American Society for Hematology, www.ash.org
2. Trefor Higgins, Melissa Mack and Annu Khajuria, Comparison of two methods for the quantification and identification of hemoglobin variants. Clinical Biochemistry. 2009 May;42(7-8):701-5. Epub 2009 Jan 23.
3. Van Delft P, Lenters E, Bakker-Verweij M, de Korte M, Baylan U, Harteveld CL, Giordano PC. Evaluating five dedicated automatic devices for haemoglobinopathy diagnostics in multi-ethnic populations. Int J Lab Hematol. 2009 Oct;31(5):484-95. Epub 2009 Apr 17.

Contributed by Oana Mihaela Radu, MD and Dmitriy Gutkin, MD, PhD