Holotranscobalamin (holo-TC) is a transcobalamin-vitamin B12 complex currently being investigated as a diagnostic test (e.g., HOLO TC RIA, Axis-Shield Active-B 12) for vitamin B12 deficiency in symptomatic and at-risk populations. 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.
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 the elderly. 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.
Measurement of holotranscobalamin in the diagnosis and management of Vitamin B12 deficiency is considered investigational.
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We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits, or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
There is a lack of evidence 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. Evidence of the clinical utility of the test is lacking.
Heil, S., de Jonge, R., Maurits, C., van Wijnen, M., Heiner-Fokkema, R., Kobold, A., et al. (2012). Screening for metabolic vitamin B12 deficiency by holotranscobalamin in patients suspected of vitamin B12 deficiency: a multicentre study. Annals of Clinical Biochemistry, 49, 184-189. (Level 4 evidence)
National Institute for Health and Care Excellence (2015, September). Medtech innovation briefing: Active B12 assay for diagnosing vitamin B12 deficiency. Retrieved May 17, 2017 from www.nice.org.
Nexo, E., & Hoffman-Lücke, E. (2011). Holotranscobalamin, a marker of vitamin B-12 status: analytical aspects and clinical utility. American Journal of Clinical Nutrition, 94 (1), 359S-365S. (Level 5 evidence)
Sobczyńska-Malefora, A., Gorska, R., Pelisser, M., Ruwona, P., Witchlow, B., & Harrington, D.J. (2014). An audit of holotranscobalamin (“Active” B12) and methylmalonic acid assays for the assessment of vitamin B12 status: application in a mixed patient population. Clinical Biochemistry, 47 (1-2), 82-86. Abstract retrieved May 25, 2018 from PubMed database.
U. S. Food and Drug Administration. (December 2011). Center for Devices and Radiologic Health. 510(k) Substantial equivalence determination decision summary k112443. Received September 2, 2015 from http://www.accessdata.fda.gov.
U. S. Food and Drug Administration. (March 2013). Center for Devices and Radiologic Health. 510(k) Substantial equivalence determination decision summary k121946. Received September 2, 2015 from http://www.accessdata.fda.gov.
Valente, E., Scott, J., Ueland, P., Cunningham, C., Casey, M., & Molloy, A. (2011). Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B12 status in the elderly. Clinical Chemistry, 57 (6), 856-863. (Level 4 evidence)
ORIGINAL EFFECTIVE DATE: 4/4/2011
MOST RECENT REVIEW DATE: 3/11/2021
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