Background: Hemoglobin A1c is used to evaluate the glycemic control in patients with diabetes and is a risk marker for chronic complications of diabetes. Hemoglobin variants are reported to falsely lower or increase hemoglobin A1c test results. We present a case report of a patient with diabetes with discrepancy between fasting plasma glucose and hemoglobin A1c due to the presence of hemoglobin Himeji, a clinically silent and very rare hemoglobinopathy.
Case presentation: A 76-year-old white woman, born and living in Portugal, with type 2 diabetes presented to the family physician for a routine visit. She had no active complaints, including history or symptoms of hypoglycemia, and her physical examination was unremarkable. A review of her laboratory data showed fasting plasma glucose of 190 mg/dL and a hemoglobin A1c of 4.1%. The remaining blood test results were clinically insignificant; a further review of her laboratory data over the past 4 years revealed that her fasting plasma glucose had ranged from 130 to 250 mg/dL and hemoglobin A1c was consistently lower than 5%. A study of hemoglobins detected 32.8% of abnormal hemoglobin. Genetic sequencing identified a heterozygous mutation compatible with hemoglobin Himeji (c.422C>A; p.Ala141Asp). We tracked her family (three sons, six grandchildren, and two greatgrandchildren) for the presence of this hemoglobin variant, but none had this hemoglobinopathy.
Conclusions: Despite the advantages of hemoglobin A1c in the follow-up and treatment of diabetes, the factors that interfere with its results must be known to ensure a correct estimation of the degree of glycemic control and a proper management of the disease. Therefore, health professionals should suspect the existence of hemoglobin variants when: the hemoglobin A1c value is above 15% or below the lower limit of its reference interval; there is a significant modification in its result coinciding with a change in assay methods; and there is a low correlation between plasma glucose and hemoglobin A1c. In patients with hemoglobin Himeji, alternate ways of monitoring glycemic control (fructosamine or glycated serum albumin) should be used.
Keywords: Diabetes mellitus; Hemoglobin A1c; Hemoglobin Himeji; Hemoglobinopathies; Mutations.