False-normal vitamin B12 results in a patient with pernicious anaemia

Pernicious anaemia is a common autoimmune disorder with a prevalence of approximately 4% amongst Europeans. If untreated, it can result in permanent neurological disability or death. Central to the diagnosis is establishing the presence of vitamin B12 deficiency. Concern has been raised recently regarding false-normal results obtained with competitive-binding vitamin B12 assays performed on automated biochemistry platforms in patients with pernicious anaemia due to the presence of interfering anti-intrinsic factor antibodies in the patient sample. We report a case in which diagnosis of pernicious anaemia was delayed due to false-normal vitamin B12 results. Questioning the results in light of high pre-test probability, and knowledge of the role of functional markers of vitamin B12 deficiency enabled the correct diagnosis to be made so that effective treatment could be initiated. It is crucial that those who frequently request vitamin B12 are aware of the potential problems with the available assays and how these problems can be addressed. We suggest that all patients with normal vitamin B12 levels where there is a high clinical suspicion for deficiency such as a macrocytic anaemia, neurological symptoms or megaloblastic bone marrow should have a functional assay of vitamin B12 (plasma homocysteine or methylmalonic acid) checked to further investigate for vitamin B12 deficiency.