Which factors are associated to hypermanganesemia in patients with long-term parenteral nutrition?

Abstract

In patients receiving long-term parenteral nutrition (PN), high blood concentrations of manganese (Mn) have been reported and associated with cholestatic disease and/or extrapyramidal symptoms. Aim: To examine the relation between plasma Mn concentrations, hepatic enzymes abnormalities, systemic inflammatory markers and importance of PN supply in patients which need long-term PN. Methods: Plasma Mn concentrations, transaminases (GOT and GPT), alkalin phosphatases (AP), gammaglutamyltranspeptidases (GGT), total and conjugated bilirubin, prothrombin time, as well as C-reactive protein, erythrocyte sedimentation rate (ESR), tumor necrosis factor-alpha (TNF) and interleukin 6 levels, soluble receptors of IL2 (as a parameter for lymphocyte activation) and, blood and 24hours-urinary neopterin concentrations (as markers of monocyte/macrophage activation) were determined in 18 patients (aged 53.8 ± 14.5 years; m ± SD) receiving long-term PN for more than 6 months (mean Mn supply; 0.119 ± 0.017 lamol/kg/day), and 9 healthy subjects (controls; aged 44.3 ± 20.3 years). In addition, brain magnetic resonance imaging (MRI) and careful neurologic clinical examination were performed in 10 patients. Results: Mn concentrations were higher in PN patients than in controls (1.9 ± 0.9 vs 0.9-+0.5 pg/L; P < 0.01) and positively correlated to the importance of PN support, GOT (r = 0.4, P < 0.01) and GPT (r = 0.34, P < 0.05) levels, AP (r = 0.53, P < 0.0001) and GGT (r = 0.32, P < 0.05) concentrations, as well as to ESR (r = 0.67, P < 0.0001), TNF (r = 0.33, P < 0.05), blood (r = 0.42, P < 0.05) and 24h-urinary (r = 0.7, P < 0.01) neopterin. Plasma Mn was negatively correlated to prothrombin time (r = -0.44, P < 0.01) but was not linked to bilirubin concentrations. Importance of PN support was positively correlated to inflammatory markers and to hepatic enzymes abnormalities, the later being positively correlated to each others. All patients investigated by MRI showed hyperintense basal ganglia on Tl-weighted images suggesting brain Mn deposition, but only one (aged 74 years and receiving PN since 1988) had slight clinical extrapyramidal symptoms. Conclusion: In patients receiving long-term PN, sustained inflammatory syndrome may favour hypermanganesemia through (1) cholestatic liver disease and thereby decreased Mn biliary excretion, (2) high nutritional requirements (responsible for increased Mn supply), and/or modified Mn metabolism or body distribution. Whereas Mn brain deposition seems frequent, neurologic complications appeared marginal.