Paper
Persistently increased vitamin B12 concentration due to cobalamin macrocomplexes: a case report and review of the literature
Published Jan 13, 2020 · J. A. D. Rodríguez, R. Mullor, María I. Pastor García
Clinical Chemistry and Laboratory Medicine (CCLM)
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Abstract
A 73-year-old woman was referred to the Internal Medicine department by the general practitioner due to persistently increased vitamin B12 concentrations (cobalamin) above 1476 pmol/L during the last 2 years. No other remarkable information was reported. Written informed consent was obtained from the patient. The physical exploration allowed excluding lymphadenopathies, splenomegaly and hepatomegaly. Neurologic examination was normal. The last fasting biochemical control showed a normal complete blood count (CBC) (no signs of dysplasia in a peripheral blood smear) and a normal general metabolic panel, including iron profile, liver panel, folate and 25-hydroxyvitamin D. Estimated glomerular filtration rate (eGFR, CDK-EPI 2009) was 87 mL/min/1.73 m2. Serum cobalamin was quantified using a chemiluminescent microparticle immunoassay on the Architect i2000 platform (Abbott Diagnostics, USA), yielding a result of >1476 pmol/L (normal: 134–651 pmol/L). Given the persistent elevation of serum cobalamin, with no other symptom or biochemical alteration, and having excluded the possibility of being supplemented, different biomarker panels were requested: tumor biomarkers, serology and autoimmunity panel. All of them were negative. Before further testing, the requesting physician contacted the laboratory manager, who decided to perform an interference study in order to rule out a spurious cobalamin result. Cobalamin is an essential micronutrient that plays an essential role in the monocarbon metabolism, by transforming methyltetrahydrofolate into tetrahydrofolate for the synthesis of DNA and fatty acid metabolism. In the blood, it binds to transcobalamin (TC) II or haptocorrin (HC). Although most cobalamin laboratory requests are oriented to the search of a deficiency, it has been reported that high cobalamin levels are unexpectedly found in 7–17% of patients who are studied with a suspicion of deficiency [1, 2]. In the absence of supplementation, high cobalamin concentrations reflect an alteration in cobalamin metabolism or an analytical interference. The etiopathogenesis of the metabolic alteration is generally multifactorial. One of the main causes is the increase in serum concentrations of the main carrier proteins, TC and HC, due to an increase in their synthesis or a decrease in their clearance [2]. Other reasons could be the low affinity of TC for cobalamin and the subsequent decrease in their tissue capture, or the release of cobalamin from the liver storages. Different diseases have been well associated with high levels of cobalamin, such as myeloproliferative syndromes (chronic myeloid leukemia, polycythemia vera), the autoimmune lymphoproliferative syndrome and the fibrolaminar hepatocellular carcinoma. Other pathologies with a likely association are cancer and metastasis of unknown origin, liver or kidney disease and the presence of anti-TC antibodies [3]. The relationship *Corresponding author: José A. Delgado Rodríguez, Department of Laboratory Medicine, Hospital Universitari Son Espases, Ctra. de Valldemossa, 79, 07010 Palma, Balearic Islands, Mallorca, Spain, Phone: +34 871205876, E-mail: jose.delgado@ssib.es María I. Pastor García: Department of Laboratory Medicine, Hospital Universitari Son Espases, Ctra. de Valldemossa, Mallorca, Spain Josep Miquel Bauça and Antònia Barceló: Department of Laboratory Medicine, Hospital Universitari Son Espases, Ctra. de Valldemossa, Mallorca, Spain; and Institut d’Investigació Sanitària de les Illes Balears (IdISBa), Palma, Spain Ramón Vidal Mullor: Department of Internal Medicine, Hospital Universitari Son Espases, Palma, Balearic Islands, Spain Clin Chem Lab Med 2020; 58(10): e237–e239
Case ReportHigh vitamin B12 levels in a 73-year-old woman were due to cobalamin macrocomplexes, not a deficiency or supplementation.
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