Gastric juice in congenital pernicious anemia contains no immunoreactive intrinsic factor molecule: study of three kindreds with variable ages at presentation, including a patient first diagnosed in adulthood.

The mechanism responsible for the isolated intrinsic factor deficiency in congenital pernicious anemia is unknown. A new second-antibody radioimmunoassay capable of recognizing intrinsic factor independent of the molecule's ability to bind added cobalamin was used to study six patients from three kindreds with this disorder. One of the patients was first diagnosed at age 23 because of unusual circumstances in her case; yet the other patients also demonstrated great age variability at presentation of this presumably congenital disorder, even within the same kindred. The radioimmunoassay failed to detect immunoreactive intrinsic factor in any of the six patients, suggesting that elaboration of an abnormal molecule was not the pathogenetic mechanism. An unexpected incidental finding, contrasting with this observation in congenital pernicious anemia, was immunologic evidence that a previously described patient with familial R binder deficiency clearly elaborated an abnormal R binder molecule.