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SPURIOUSLY HIGH HBA1C DUE TO THE PRESENCE OF HAEMOGLOBIN RALEIGH: A CASE REPORT AND REVIEW OF THE LITERATURE

Abstract Case summary The described case concerns a Caucasian obese female patient who presented with a spuriously high haemoglobin A1c value of 45.6% (ref. range 4.0-6.1%), as measured with one of the three cation-exchange chromatography methods used. Re-evaluation of serum haemoglobin A1c and glycohaemoglobin with immunoassay and affinity binding chromatography resulted in normal levels (4.14% (ref. range 4.0-6.0%) and 4.3% (ref. range <6%), respectively). In addition, the patient’s serum fructosamine value – another indicator of plasma glucose concentration over time – was low (184 μmol/l (ref. range 205-285 μmol/l)). Genetic testing lead to the identification of an uncommon and clinically silent haemoglobin variant, designated Raleigh, in which a mutation of the β chain results in the replacement of the N-terminal valine by acetylated alanine. Discussion Some Hb variants give rise to analytical errors in the HbA1c determination (e.g. co-elution of haemoglobin Raleigh with HbA1c in cation-exchange chromatography), whereas other Hb variants are associated with a shorter RBC turnover or a different glycation rate, which causes interpretation problems (e.g. no glycation of the acetylated alanine in haemoglobin Raleigh). Conclusion This article illustrates the difficulties in diabetes management in patients with a haemoglobin variant and it provides the clinician with a diagnostic flow chart for dealing with suspicious haemoglobin A1c values.