Seminars in Vascular Medicine 2005; 5: 140-155 DOI: 10.1055/s-2005-872399
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001 USA.
Novel and Established Markers of Cobalamin Deficiency: Complementary or Exclusive Diagnostic Strategies
Jörn Schneede1,2, Per Magne Ueland2
1 Department of Clinical Chemistry, Umeå University, Umeå, Sweden 2 Locus for Homocysteine and Related Vitamins, University of Bergen, Bergen, Norway

ABSTRACT

New developments in diagnostic markers and a better understanding of the limitations of traditional diagnostic strategies have allowed diagnosis of earlier stages and atypical forms of cobalamin deficiency. Still, there are no generally accepted guidelines for the definition, diagnosis, treatment, and follow-up of cobalamin deficiency. The new trend toward defining cobalamin deficiency purely on the basis of biochemical test outcomes in the absence of overt clinical signs and symptoms could, however, be problematic and may result in overdiagnosis and overtreatment. Use of metabolic markers for the assessment of cobalamin deficiency allows the demonstration of tissue deficiency, but the establishment of the cause of deficiency should also be part of the diagnostic approach. Four groups of diagnostic tests are currently available and these include total cobalamin and cobalamin fractions (such as holo-transcobalamin), tests of gastrointestinal dysfunction, tests of metabolic function, and different gene tests. Among the available tests, only homocysteine, methylmalonic acid, holo-transcobalamin, and possibly methylcitric acid are considered to be useful in clinical practice to add to cobalamin. Gastrointestinal function tests may identify the cause of cobalamin deficiency, whereas the diagnostic usefulness of genetic testing needs to be evaluated. This article provides an overview of recent developments and a reappraisal of novel and established diagnostic markers for cobalamin deficiency.

KEYWORDS

Diagnostic markers - cobalamin deficiency - holoTC - homocysteine - methylmalonic acid