Haemoglobin O Padova and falsely low haemoglobin A(1c) in a patient with type I diabetes

Abstract

Glycated haemoglobin (HbA(1c)) measured by high performance liquid chromatography (HPLC) in a 20 year old female with insulin dependent diabetes mellitus was consistently within the normal range although her daily blood glucose values were > 11.1 mmol/l. HbA(1c) measured by immunoagglutination and fructosamine was elevated and correlated with the patient's blood glucose values. The HPLC chromatogram showed an additional peak at HbA(o). Electrophoresis of haemoglobin on citrate agar gel revealed an abnormal haemoglobin anodal of HbS. Cellulose acetate electrophoresis and isoelectric focusing demonstrated an additional haemoglobin migrating close to HbA2. Amino acid analysis and DNA sequencing revealed an α 30 (B11) Glu→Lys replacement, that is, haemoglobin O Padova. Investigations of two family members without diabetes revealed the same rare haemoglobin variant. This case showed that this silent haemoglobin mutation caused an additional peak and falsely low HbA(1c) values when measured by HPLC, the gold standard for this evaluation.