Hemoglobin hafnia: alpha 2 (beta 116 (G18) His----Gln)2; a new hemoglobin variant mistaken for glycated hemoglobin.

Isoelectric focusing of hemolysate from patients with diabetes mellitus is routinely performed to measure their level of HbA1c (glycated hemoglobin). For a 6 year old boy with diabetes mellitus this analysis showed an HbA1c fraction of approx. 50%, which is very unlikely to occur. The possibility of a hemoglobin variant was considered, and by HPLC-separation the presence of two different beta-chains was shown. One tryptic fragment was found to deviate from the normal, and amino-acid analysis and sequence determination revealed the following amino-acid substitution: beta 116 His----Gln. It is the first reported mutation at this position. Functional studies showed almost normal behaviour, consistent with the fact that the affected persons are without any symptoms. In a family survey we found five nondiabetic members with an abnormality similar to the proband. For the variant we chose the name Hafnia, which is Latin for Copenhagen.