Dr. Ron’s Research Review – January 6, 2016

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This week’s research review focuses on elevated B12 levels.

Hypercobalaminemia is a frequent and underestimated anomaly. Clinically, it can be paradoxically accompanied by signs of deficiency, reflecting a functional deficiency linked to qualitative abnormalities, which are related to defects in tissue uptake and action of vitamin B12. While low serum cobalamin levels do not necessarily imply deficiency, an abnormally high serum cobalamin level forms a warning sign requiring exclusion of a number of serious underlying pathologies, including solid neoplasms, hematological malignancies and liver and kidney diseases. Functional cobalamin deficiency can thus occur at any serum level. (Andrès et al., 2013)

More than 8% of patients examined for vitamin B12 deficiency unexpectedly have increased plasma levels. Since a number of the associated diseases are critical and life-threatening, the strategy promotes the concept of 'think the worst first'. It is important to realise that high cobalamin levels can be an unspecific marker for cancer. If this can be ruled out, diseases of the liver and kidney should be considered. (Arendt and Nexo, 2013)

In this study, characteristic of patients with serum vitamin B12 levels higher than 2500 pmol/L (high B12) were studied. B12 treatment was the main cause of high B12. In patients with repeatedly high B12 levels, immune complexes were detected in approximately 25% of samples. An association with autoimmune or hematological disorders was observed. (Remacha et al., 2013)

Dr. Ron


 

Articles

The pathophysiology of elevated vitamin B12 in clinical practice.
            (Andrès et al., 2013) Download
Hypercobalaminemia (high serum vitamin B12 levels) is a frequent and underestimated anomaly. Clinically, it can be paradoxically accompanied by signs of deficiency, reflecting a functional deficiency linked to qualitative abnormalities, which are related to defects in tissue uptake and action of vitamin B12. The aetiological profile of high serum cobalamin predominantly encompasses severe disease entities for which early diagnosis is critical for prognosis. These entities are essentially comprised of solid neoplasms, haematological malignancies and liver and kidney diseases. This review reflects the potential importance of the vitamin B12 assay as an early diagnostic marker of these diseases. A codified approach is needed to determine the potential indications of a search for high serum cobalamin and the practical clinical strategy to adopt upon discovery of elevated cobalamin levels. While low serum cobalamin levels do not necessarily imply deficiency, an abnormally high serum cobalamin level forms a warning sign requiring exclusion of a number of serious underlying pathologies. Functional cobalamin deficiency can thus occur at any serum level.

Unexpected high plasma cobalamin : proposal for a diagnostic strategy.
            (Arendt and Nexo, 2013) Download
It is well-established that more than 8% of patients examined for vitamin B12 deficiency unexpectedly have increased plasma levels of the vitamin, but so far there are no guidelines for the clinical interpretation of such findings. In this review, we summarise known associations between high plasma cobalamin and diseases. We report associations mainly with cancer, liver and kidney diseases, but also with a number of other diagnostic entities. The pathogenic background is poorly understood and is likely to be multi-factorial, involving increased concentrations of one or both of the circulating cobalamin binding proteins, transcobalamin and haptocorrin. Based on current knowledge, we suggest a strategy for the clinical interpretation of unexpected high plasma cobalamin. Since a number of the associated diseases are critical and life-threatening, the strategy promotes the concept of 'think the worst first'. It is important to realise that high cobalamin levels can be an unspecific marker for cancer. If this can be ruled out, diseases of the liver and kidney should be considered.


 

Immune complexes and persistent high levels of serum vitamin B12.
            (Remacha et al., 2013) Download
INTRODUCTION: Patients with persistent high levels of serum vitamin B12 were often referred to Hematology departments. In this study, characteristic of patients with serum vitamin B12 levels higher than 2500 pmol/L (high B12) were studied. METHODS: Prevalence of high B12 was evaluated during a 10-month period. Samples with high B12 were incubated with polyethylene glycol (PEG) and a new measurement of vitamin B12 was carried out using the supernatant. As a pilot study, 26 frozen samples with high B12 were evaluated for changes in vitamin B12 after PEG. Moreover, a prospective study was carried out during three consecutive months. Size exclusion chromatography was employed to demonstrate the presence of immune complexes (ICs) with plasma vitamin B12-binding proteins in some serum samples with high B12. RESULTS: Prevalence of high B12 was 1.3%. Results from 26 frozen samples and from a prospective study (28 cases) showed that undergoing vitamin B12 treatment was the main cause of high B12. However, ICs were detected in 10 frozen samples and in seven cases (25%) of the prospective study, respectively. Serum vitamin B12 decreased to normal values after precipitation with PEG, and size exclusion chromatography confirmed ICs. An association with autoimmune or hematological disorders was observed. CONCLUSIONS: In patients with repeatedly high B12 levels, ICs were detected in approximately 25% of samples. Precipitation with PEG is an easy method to confirm the presence of ICs and to evaluate serum vitamin B12 levels in these patients.

 

 

References

Andrès, E, et al. (2013), ‘The pathophysiology of elevated vitamin B12 in clinical practice.’, QJM, 106 (6), 505-15. PubMedID: 23447660
Arendt, JF and E Nexo (2013), ‘Unexpected high plasma cobalamin : proposal for a diagnostic strategy.’, Clin Chem Lab Med, 51 (3), 489-96. PubMedID: 23241600
Remacha, AF, et al. (2013), ‘Immune complexes and persistent high levels of serum vitamin B12.’, Int J Lab Hematol, PubMedID: 23998297