On the diagnosis of cobalamin malabsorption. With special reference to the identification of patients in whom substitution treatment is warranted

Abstract

There is a well-known overlap in serum concentrations of cobalamins between healthy individuals and patients with deficiency. Anaemia and macrocytosis are sometimes lacking in patients with neurological symptoms and macrocytosis may be absent in anaemia caused by cobalamin deficiency. Thus, it is sometimes difficult to assess whether a low or low normal serum concentration of cobalamins is a sign of disease or not. The aims of the study were to study different supplementary tests which can be used to support or discard the suspicion of cobalamin malabsorption/deficiency.As cobalamin deficiency in adults with very few exceptions is caused by malabsorption all patients referred to our clinic because of suspected cobalamin deficiency were extensively investigated with respect to the gastrointestinal tract with gastroscopy, the Schilling test and a protein-bound cobalamin absorption test. Serum pepsinogen A and C, gastrin and antibodies to H+,K+-ATPase were used as indirect tests of the function of the gastric body mucosa. These tests were compared with the serum concentrations of methylmalonic acid (MMA) and total homocysteine (Hcy), indicators of intracellular deficiency, and plasma holotranscobalamin, the biologically active cobalamins. The sensitivity and specificity of the tests to identify patients with conditions compatible with cobalamin malabsorptin/deficiency were calculated.Gastric body atrophy was found as the underlying cause of malabsorption/deficiency in about 90% of the patients. Serum pepsinogen A combined with serum gastrin or serum pepsinogen C had very high sensitivity for severe to moderate gastric body atrophy (about 0.95) and high specificity (1.0). These combinations of tests also identified virtually all patients with gastric body atrophy and positive metabolite tests. Moreover, elevated serum concentrations of the metabolite tests were found in approximately 15% of the patients without conditions compatible with cobalamin malabsorption. The serum concentrations of MMA and Hcy decreased in virtually all patients without conditions compatible with cobalamin malabsorption following treatment with cobalamin. These results call into question the high specificity for these tests as reported in the litterature.