False Low HbA1c in a Diabetic Patient with HbD-β-thalassemia Trait:A Diagnostic Pitfall Due toHemoglobin Variant Interference

HbA1c is the standard marker to assess glycemic control in diabetes mellitus. However, hemoglobin (Hb) variants can interfere with HbA1c measurements, especially with methods like ion-exchange HPLC, leading to falsely low values and potential misdiagnosis. We report a case of a 52-year-old male who presented in our outpatient department with features of hyperglycemia. Despite clinical and biochemical features consistent with diabetes, his HbA1c was reported as 0%. Further evaluation revealed elevated serum fructosamine 540 µmol/L, and Hb electrophoresis showed a prominent unknownpeak at 3.92 minutes (75%), consistent with HbD-β-thalassemia heterozygous state. HbD, particularly HbD-Punjab, is a variant of the β-globin chain characterized by the replacement of a glutamic acid by glutamine at codon 121. In this case, the HbD-β-thalassemia heterozygous variant led to a significant analytical interference, causing a misleadingly zero HbA1c report in a diabetic patient. Awareness of such interference due to Hb variants is crucial to avoid diagnostic errors and treatment delays in diabetic patients. Inappropriate HbA1c values, particularly very low or undetectable levels in the context of hyperglycemia, should prompt evaluation for hemoglobinopathies. Alternate glycemic markers like fructosamine and glycated albumin, along with careful clinical judgment, are essential in such scenarios.