Vitamin B12 Deficiency - New trends in biomarkers and diagnostic strategies
1Department of Clinical Biochemistry, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
Today, the clinical aims are to
identify patients before severe symptoms of vitamin B12 deficiency
have developed. Thus an impaired vitamin B12 status has almost become
a “biochemical” rather than a clinical diagnosis.
An impaired status should be suspected in patients with uncharacteristic symptoms together with one or more of the following conditions: aged above 65 years, consuming little or no food of animal origin, gastrointestinal symptoms, treated with acid reducing agents or possibly metformin.
Measurement of total plasma cobalamin is the test most frequently employed. It has its limitations mainly because a low normal level may not exclude an impaired vitamin B12 status. Two biochemical markers have been introduced; homocysteine and notably methylmalonic acid (MMA). MMA has two limitations. It is influenced by kidney function, and, it requests equipment not available in all laboratories.
More recently measurement of the part of circulating cobalamin available to the cells, holotranscobalamin (holoTC , active B12) has been introduces as has an algorithm including all four parameters, total cobalamin, holoTC, homocysteine and MMA.
In our lab, we suggest a strategy where total cobalamin is used as first line analysis and supplemented with MMA if total cobalamin is “in the grey area”. Measurement of holoTC instead of total cobalamin is judged to be preferable, but it demands the availability of the analyte on automatic platforms and a cost close to that of measuring total cobalamin.
Once an impaired vitamin B12 status has been diagnosed, there is a need to explore if this is caused by an impaired capacity to absorb the vitamin. Using the CobaSorb test holoTC is measured before and after two days’ intake of a test dose of the vitamin. An increase in holoTC indicates the capacity to absorb the vitamin.