the amino acid glutamic with lysine at position 26 ( E26K ) due to a single point mutation in the β chain . 7 The HbE variant was discovered in 1954 , and there are still doubts about many aspects of its pathophysiology . HbE diseases could be heterozygotes ( AE ), homozygotes ( EE ), and compound heterozygous states ( e . g ., HbE / β-thalassemia , sickle cell / HbE disease ). Both heterozygotes and homozygotes are asymptomatic with a lower degree of anemia and have microcytic and hypochromic RBCs . However , when β E allele is associated with a β-thalassemia mutation in the compound heterozygous state , a variable – usually severe anemia – will occur , with Hb levels ranging from 3 to 11 g / dl . 4
Figure 2 : Hb Profile
Considering the history , clinical findings , and laboratory test results , our case is most likely diagnosed as homozygous HbE disease , which causes only a mild , usually asymptomatic anemia with microcytosis and erythrocytosis . Peripheral smear examination showed spherocytes . 8 Spherocytosis could be related to either membrane damage due to oxidation or elimination of precipitated , unbalanced β globin chain and / or crystallized HbE . 8 If the HbA1c method is affected by the presence of HbE , using HbA1c in glycemic control in the endemic areas for HbE should be carefully reconsidered . 7
HbE disease does not impact the immunoassay technique of HbA1c estimation , as the mutation is away from the site of the antibody reaction . However , it affects the ion-exchange HPLC method , as the mutation leads to alter the ionic charges on the Hb . 9
Double heterozygous HbE / β-thalassemia is a differential diagnosis in this case . Anemia , the presence of HbE by Hb electrophoresis , and target cells on peripheral blood smear have been described in both HbE disease and HbE / β-thalassemia . 10
Since HbE / β-thalassemia cannot be entirely excluded in this case , genetic testing has been done to the patient . The final patient diagnosis for our patient is Homozygous Hb disease based on Beta
Globin Gene Sequencing which leads to absence of HbA1c by cationic change HPLC ( D100 ).
Conclusion
When evaluating a patient ’ s HbA1c values it is important to consider the limitations of analytic methodology and possible hemoglobin variants , particularly in the context of non-congruence between a patient ’ s glycemic pattern and the reported HbA1c . Different HbA1c methods and / or alternative markers to assess long-term glycemic control in patients with a hemoglobin variant should also be considered .
References
Email ams @ arkmed . org for a complete list of references .
179 • The Journal of the Arkansas Medical Society www . ArkMed . org