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DESCRIPTIONVitamin B12 (i.e., cobalamin) is an essential vitamin that is required for one-carbon metabolism and cell division. Cobalamin deficiency can result from nutritional/dietary deficiencies (most common among the vegetarian and the elderly), malabsorption of vitamin B12 (seen after gastrectomy or associated with autoantibodies [i.e., pernicious anemia]), or other relatively uncommon gastrointestinal conditions (i.e. Whipple’s disease, Zollinger Ellison syndrome, etc.). 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 disappear promptly after treatment, neurologic disorders may become permanent if left untreated.
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 level of MMA and homocysteine are elevated, and have been investigated as surrogate markers.
There has also been 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 holo-transcobalamin, 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 Axis-Shield HoloTC RIA is an example of a radioimmunoassay for holo-TC that was cleared for marketing by the U.S. Food and Drug Administration (FDA) in 2004 with the following labeled indication for use:
“The Axis-Shield HoloTC RIA is an in vitro diagnostic assay for quantitative measurement of the fraction of cobalamin (vitamin B12) bound to the carrier protein transcobalamin in the human serum or plasma. Measurements obtained by this device are used in the diagnosis and treatment of vitamin B12 deficiency.”
In November 2006, the device “Axis-Shield HoloTC Assay” (Axis-Shield, Dundee, UK),an enzyme immunoassay for holo-TC, was cleared for marketing by the FDA through the 510(k) process. The FDA determined that this device was substantially equivalent to existing devices for use in:
POLICYMeasurement of holotranscobalamin is considered investigational in the diagnosis and management of Vitamin B12 deficiency.
POLICY EXCEPTIONSFederal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.
POLICY GUIDELINESInvestigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
POLICY HISTORY7/21/2005: Approved by Medical Policy Advisory Committee (MPAC)
4/1/2008: Policy reviewed, no changes
09/09/2010: Policy description updated regarding available devices. FEP verbiage added to the Policy Exceptions section.
09/23/2011: Policy reviewed; no changes.
09/27/2012: Policy reviewed; no changes.
10/22/2013: Policy reviewed; no changes.
07/23/2015: Code Reference section updated for ICD-10.
12/31/2015: Investigative definition updated in policy guidelines. Code Reference section updated to add CPT code 84999.
SOURCE(S)Blue Cross Blue Shield Association policy # 2.04.39
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.