Pitfalls in the Diagnosis of Vitamin B12 Deficiency

Vitamin B12 deficiency is a well-described disorder with a spectrum of manifestations ranging from macrocytic anemia to neuropsychiatric disorders including depression, dementia, and subacute combined degeneration of the spinal cord. Lack of vitamin B12 arises from insufficient intake or malabsorption. In clinical practice, serum total cobalamin (Cbl) levels are the initial test of choice for detecting B12 deficiency as they are widely available and cost-effective. However, this test is limited in specificity and sensitivity, missing many patients within the laboratory “gray zone” of deficiency. Measurements of serum methylmalonic acid (MMA) and homocysteine (Hcy) levels, which accumulate in B12 deficiency, become useful when Cbl levels are equivocal but clinical suspicion remains high. Early vitamin B12 replacement is important in preventing potentially irreversible neurologic damage. We report a case of a 75 year-old man presenting with symptomatic anemia, neuropsychiatric findings, and repeatedly normal serum cobalamin levels, eventually diagnosed with vitamin B12 deficiency due to pernicious anemia. This case highlights the potential difficulty in establishing this common diagnosis due to false-negative Cbl assay results. Given its high prevalence, vitamin B12 deficiency must be included in the differential diagnosis of patients with progressive neuropsychiatric findings and/or hematologic derangements as rapid diagnosis and supplementation may prevent permanent complications.