A variant hemoglobin found by dissociation of blood glucose from HbA1c on routine physical examination

: Discrepancy between HbA1c measured by routine HPLC and blood glucose was observed in four out of 340 persons on physical examination. We investigated whether this discrepancy was due to abnormal hemoglobin. HbA1c was measured by routine HPLC and latex agglutination. For further examinations, a hemoglobin specimen was analyzed by weak cation-exchange column(PolyCAT A) chromatography, ESI/MS and MS/MS. HbA1c levels measured by HPLC were about half of those measured by latex agglutination. An abnormal peak between HbA1c and HbA0 was detected on HPLC chromatography in three consanguineous persons. The abnormal hemoglobin from one of the related person was also confirmed by PolyCAT A chromatography. The hemoglobin specimen contained almost same amounts of normal HbA0 and abnormal Hb. Analyses of the globin by ESI/MS and MS/MS revealed that glutamate at the 22nd amino acid residue of the beta-chain was replaced by alanine. This variant was the same as HbG-Coushatta[beta 22(B4) Glu-->Ala]. Family studies showed that the variant was inherited as a dominant trait. The dissociation observed in the case was due to a presence of a variant hemoglobin. In the other case HbA1c levels measured by the two methods were similarly low, and no abnormal peak was observed on HPLC chromatography. Similar studies on the hemoglobin of this case did not disclose any abnormalities. The low values of HbA1c of this case were considered in the lowest region of the normal range.