Serum methylmalonic acid and total homocysteine in patients with suspected cobalamin deficiency: A clinical study based on gastrointestinal histopathological findings

Abstract

We compared the sensitivity and specificity of the two metabolite tests, methylmalonic acid (MMA) and total homocysteine (Hcy) in serum, and serum cobalamin (Cbl) in patients referred to our hospital because of suspected cobalamin deficiency and a serum cobala-min value at the referring unit <200 pmol/L. All 111 patients included were investigated using upper gastrointestinal endoscopy with biopsy specimens taken from the gastric and duodenal mucosa to find a morphological basis for cobalamin malabsorption as well as the Schilling test for the validation of the serum tests. All patients were treated with cobalamin and new blood samples were taken after 4 weeks. We found no difference in sensitivity and specificity between serum MMA, Hcy, and Cbl in identifying patients with and without conditions compatible with cobalamin malabsorption. Elevated serum MMA and Hcy were also found in about 15% of the group of patients with normal Schilling tests and without a morphological basis for cobalamin malabsorption. Moreover, most patients in this group responded with decreased values of the metabolite tests following cobala-min treatment, suggesting that neither elevated metabolites nor a decrease in these values following cobalamin treatment are specific for cobalamin deficiency. Am. J. He-matol. 56:230-238, 1997.

The marker of cobalamin deficiency, plasma methylmalonic acid, correlates to plasma creatinine

“…The study by Lindgren et al . [26] and our findings emphasize that the interpretation of P‐MMA is still a key question.…”

“…A recent study by Lindgren et al . [26] did not find a higher specificity and sensitivity of increased P‐MMA compared with low plasma cobalamins for identifying patients with conditions compatible with cobalamin malabsorption. These findings are in strong contrast with earlier studies claiming much higher sensitivity of abnormal P‐MMA concentrations compared with low plasma cobalamins [22, 27, 28].…”

Advantages of serum pepsinogen A combined with gastrin or pepsinogen C as first‐line analytes in the evaluation of suspected cobalamin deficiency: a study in patients previously not subjected to gastrointestinal surgery

“…Since the elevation of the results for the two metabolite tests does not occur at the same time in early deficiency, the simultaneous use of both tests is recommended [34, 35]. The benefit of adding the determination of gastrin with a decision limit of 100 pmol L −1 (twice the upper normal reference limit) to that of pepsinogen A in a previous study was not convincing [24].…”

Elevated serum methylmalonic acid. How much comes from cobalamin deficiency and how much comes from the kidneys?

“…Lindgren et al (25) Among 62 patients with normal S-creatinine and extensively investigated without any sign of cobalamin malabsorption, 10 had elevated S-MMA. These 10 had signicantly higher S-creatinine than those with S-MMA within the reference interval (p < 0.05).…”

“…All patients had serum In the study by Naurath et al [22 ], more than 80% of the 285 patients/subjects (aged 65-96 creatinine within the reference interval (60-120 mmol/L) but the group of patients with years) with initially elevated S-MMA concentrations had concentrations of serum cobalamins elevated S-MMA had a signi cantly higher mean serum creatinine concentration compared to the within the reference interval (calculated for both cobalamin and MMA on healthy volunteers, group with normal S-MMA [25 ]. This nding has now found further and substantial support 20-25 years of age).…”