False HbA1c value due to a rare variant of hemoglobin Petie Salpetriere coinherited with alpha thalassemia.

Abstract

Objectives: To describe a variant hemoglobin that interferes with HbA_1c analysis by cation exchange HPLC.

Case presentation: A 78 years-old Spanish male patient visited the Internal Medicine Clinic for a routine check-up, with HbA_1c included to screen for diabetes. He had suffered hypertension and dyslipidemia, and the patient had no previous symptoms suggestive of diabetes such as hyperglycemia, weight loss, polydipsia, polyuria or tiredness. Diabetes screening by HbA_1c measurement was assessed using cation exchange HPLC and an immunoassay point-of-care analyzer. Routine hemoglobinopathy screening was performed including CBC, HbF and HbA₂ measurement by cation exchange HPLC and capillary electrophoresis (CE). Further variant characterization was undertaken by DNA sequencing. Discordant HbA_1c results were obtained for our subject, with elevated HbA_1c of 52 mmol/mol measured by cation exchange HPLC and a normal level of 34 mmol/mol by immunoassay. Abnormal HbA_1c peak shape prompted hemoglobinopathy screening to investigate potential variant interference. A globin gene analysis was performed, and the results showed a variant hemoglobin named 'Hb Petie Salpetriere'. This variant arises from a Val → Phe substitution due to a mutation of c.103G>T of the beta-globin gene [BETA34 (B16) Val>Phe; HBB:c.103G>T].

Conclusions: This is the first reported case involving the Hb Petie Salpetriere variant in a Spanish patient. The present results show that the Hb Petie Salpetriere variant can affect the results of HbA_1c analysis through ion-exchange HPLC, but not that obtained from the latex agglutination immunoassay. Only ion-exchange HPLC suggested the presence of the Hb variant in this case, suggesting that a careful review of the resulting chromatogram might reveal a potential variant.