DESCRIPTION
Holotranscobalamin (holo-TC) is a transcobalamin-vitamin B12 complex which has been investigated as a diagnostic test for vitamin B12 deficiency in symptomatic and at-risk populations, as well as an assay for monitoring response to therapy.
Vitamin B12 (cobalamin) is an essential vitamin that is required for DNA synthesis affecting red blood cell formation and methionine synthesis affecting neurologic functioning. Cobalamin deficiency can result from nutritional deficiencies or malabsorption. Dietary insufficiency is most common among vegetarians and elderly people. Malabsorption of vitamin B12 may be associated with auto antibodies, as in pernicious anemia, or can occur after gastrectomy, or in other gastrointestinal conditions, such as celiac disease, Whipple’s disease, and Zollinger-Ellison syndrome. Clinical signs and symptoms of cobalamin deficiency include megaloblastic anemia, paresthesias and neuropathy, and psychiatric symptoms, such as irritability, dementia, depression, or psychosis. While the hematologic abnormalities promptly disappear after treatment, neurologic disorders may become permanent if treatment is delayed.
The diagnosis of cobalamin deficiency has traditionally been based on low levels of total serum cobalamin, typically less than 200 pg/mL, in conjunction with clinical evidence of disease. However, this laboratory test has been found to be poorly sensitive and specific. Therefore, attention has turned to measuring metabolites of cobalamin as a surrogate marker. For example, in humans only 2 enzymatic reactions are known to be dependent on cobalamin: the conversion of methylmalonic acid (MMA) to succinyl-CoA, and the conversion of homocysteine and folate to methionine. Therefore, in the setting of cobalamin deficiency, serum levels of MMA and homocysteine are elevated and have been investigated as surrogate markers.
There also is interest in the direct measurement of the subset of biologically-active cobalamin. Cobalamin in serum is bound to 2 proteins, transcobalamin and haptocorrin. Transcobalamin-cobalamin complex (called holotranscobalamin, or holo-TC) functions to transport cobalamin from its site of absorption in the ileum to specific receptors throughout the body. Less than 25% of the total serum cobalamin exists as holo-TC, but this is considered the clinically relevant biologically active form. Serum levels of holo-TC can be measured using a radioimmunoassay or enzyme immunoassay.
The device HoloTC RIA is an example of a radioimmunoassay for holo-TC that was cleared for marketing by the U.S. Food and Drug Administration through the 510(k) process.
POLICY
Measurement of holotranscobalamin in the diagnosis and management of Vitamin B12 deficiency is considered investigational.
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ADDITIONAL INFORMATION
There are inadequate data to establish holotranscobalamin testing as an alternative to either total serum cobalamin, or levels of MMA or homocysteine in the diagnosis of vitamin B12 deficiency. While technically feasible, and likely to have diagnostic performance that approaches that of currently utilized tests, no evidence of clinical utility has been demonstrated, neither as a screening tool in the general or at-risk population, nor as a diagnostic tool in symptomatic individuals. Evidence of the clinical utility of the test is currently lacking, and therefore the test is investigational.
SOURCES
BlueCross BlueShield Association. Medical Policy Reference Manual. (8:2010). Serum holotranscobalamin as a marker of vitamin B12 (Cobalamin) status (2.04.39). Retrieved December 28, 2010 from BlueWeb. (15 articles and / or guidelines reviewed)
ORIGINAL EFFECTIVE DATE: 4/4/2011
MOST RECENT REVIEW DATE: 4/4/2011
ID_EBA
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