Summary.
It is becoming increasingly clear that serum vitamin B12 (cobalamin) concentration is a dubious indicator of functional B12 status and, in contrast to long-standing convention, correlates poorly with haematological indices. This, in turn, has led to poorly defined reference intervals for serum B12. Patients presenting with neurological disturbance due to B12 deficiency are at risk of not being diagnosed if total reliance is placed on serum B12 levels and haematological parameters. Plasma homocysteine remethylation is uniquely placed at the metabolic end-point of B12 metabolism such that plasma total homocysteine is proving to be a sensitive marker of functional B12 status. Studies also show that plasma homocysteine correlates better with holotranscobalamin than serum B12. It is suggested that clinicians should cease to be guided by surrogate haematological markers when more specific tests of B12 deficiency, such as holotranscobalamin and total homocysteine, exist. These tests demand greater prevalence in routine diagnostic use.
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Received April 15, 2002 Accepted May 15, 2002 Published online September 4, 2002
Acknowledgements I particularly thank Dr JM Land for his appraisal of the manuscript and helpful suggestions. Grateful thanks also to Drs G Giovannoni, P Lee and H Manji for willingly allowing use of patient material. Fibroblast complementation studies provided by Professor D Rosenblatt, Division of Medical Genetics, McGill University, Montreal.
Author's address: Anthony Briddon, Neurometabolic Unit (Box 105), National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK, E-mail: anthony.briddon@uclh.org
Abbreviations and units: Cbl: cobalamin, vitamin B12; tHcy: total homocysteine; TCII: transcobalamin(II), MMA: methylmalonic acid; adomet: S-adenosyl methionine. For the sake of consistency all cobalamin values are cited as picomolar concentrations. Where necessary these have been obtained by conversion from the other commonly used mass concentration, nanogram/L, using the relationship: pmol/L × 1.35 = ng/L.
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Briddon, A. Homocysteine in the context of cobalamin metabolism and deficiency states. Amino Acids 24, 1–12 (2003). https://doi.org/10.1007/s00726-002-0319-3
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DOI: https://doi.org/10.1007/s00726-002-0319-3