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Cobalamin Analogues Are Present in Human Plasma and Can Mask Cobalamin Deficiency because Current Radioisotope Dilution Assays Are Not Specific for True Cobalamin

List of authors.
  • J. Fred Kolhouse, M.D.,
  • Haruki Kondo, M.D.,
  • Nancy C. Allen, R.N.,
  • Elaine Podell, A.B.,
  • and Robert H. Allen, M.D.

Abstract

Since R protein binds cobalamin (vitamin B12) and cobalamin analogues, whereas intrinsic factor is highly specific for true cobalamin, we compared the serum cobalamin values obtained with these proteins in radioisotope dilution assays. With R protein, eight of 21 patients with cobalamin deficiency had serum cobalamin levels (mean, 204, range, 85 to 355 pg per milliliter) that overlapped with values for 74 normal subjects (mean, 576, range, 220 to 1230). With intrinsic factor, no patient values (mean, 36, range, <10 to 78 pg per milliliter) overlapped with the normal values (mean, 322, range, 130 to 785). Paper chromatography showed that these differences were due to the presence of cobalamin analogues.

R protein constituted 51 to 85 per cent of the cobalamin-binding protein in 10 commercial serum cobalamin assay kits, which were said to contain "intrinsic factor." Human plasma contains cobalamin analogues that can mask cobalamin deficiency with current radioisotope dilution assays. (N Engl J Med 299:785–792, 1978)

Funding and Disclosures

The term "R protein" was originally devised to denote a cobalamin-binding protein in human gastric juice that was devoid of intrinsic-factor activity. It was designated as protein "R" because of its rapid mobility on electrophoresis. Subsequently, immunologically related proteins have been observed in a variety of human tissues and body fluids and have been referred to as the R proteins.

Presented in part at the annual meeting of the American Society for Clinical Investigation, San Francisco, CA, May 1, 1978.

Supported in part by a research grant (AM 21365) from the National Institutes of Health.

We are indebted to Drs. V. Michael Whitehead and William S. Beck for performing the cobalamin assays using Euglena gracilis and Lactobacillus leichmannii, respectively, to Drs. Whitehead, Eugene P. Frenkel and Bernard A. Cooper for supplying serum samples from patients with cobalamin deficiency, to Drs. Ross Langley and Everette Jones for providing information concerning their patients and to Mrs. Maria Ignacio for technical assistance.

Author Affiliations

From the divisions of Hematology and Oncology, Department of Medicine, University of Colorado Medical Center, Denver, CO 80262, where reprint requests should be addressed to Dr. Kolhouse.

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