HEMOGLOBIN RAMBAM (BETA-69[EI3]GLY-]ASP), A PITFALL IN THE ASSESSMENTOF DIABETIC CONTROL - CHARACTERIZATION BY ELECTROSPRAY MASS-SPECTROMETRY AND HPLC

Hemoglobin (Hb) Rambam, or beta 69[E13]Gly-->Asp, has been identified in a German woman also suffering from non-insulin-dependent diabetes m ellitus and chronic obstructive pulmonary disease. This is the first o bservation of this Hb variant in a German family thus far. The detaile d evaluation of its structure using electrospray mass spectrometry rev ealed new minor glycohemoglobin components and showed that the attachm ent of glucose to the beta NH2 terminus occurred at an almost identica l rate in both wild-type and mutant beta-chains. However, the introduc tion of a carboxyl group at beta 69 seems to Increase the glycation of epsilon-amino groups of lysine residues. The glycemic state in the pr opositus was well reflected by the total glycohemoglobin concentration s but not by the Hb A(1C) values, which did not reflect hemoglobin gly cation in this patient. This case demonstrates that Hb A(1C) cannot be used reliably in the management of diabetic patients carrying Hb vari ants such as Hb Rambam. Functional studies of the whole blood of the h eterozygous carrier demonstrated extremely low oxygen affinity, which may have been caused by increased 2,3-diphosphoglycerate related to ch ronic obstructive pulmonary disease and hyperthyroidism. None of the c linical symptoms could be directly associated to Hb Rambam.