Diagnosis and management of clinical and subclinical cobalamin deficiency: advances and controversies.

Major recent developments in cobalamin deficiency include issues such as the nature of food-cobalamin malabsorption, sensitivities and specificities of diagnostic tests, and emerging data on oral therapy. These have been heavily influenced by studies of subclinical deficiency, which has a much slower progression (which may be nonlinear), arises from different causes, and poses different, more public health-oriented management considerations than the less frequent but much more medically important entity of clinically expressed deficiency. Distinguishing carefully between the two deficiency states is helpful because clinical lessons and strategies derived from one may not apply equally to the other, as illustrated by controversial decisions about clinical issues such as the serum cobalamin level diagnostic of deficiency. Reassessment of diagnostic and management approaches, including improving our ability to diagnose cobalamin malabsorption, is required.