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Long term differential consequences of miglustat therapy on intestinal disaccharidases

  • Original Article
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Journal of Inherited Metabolic Disease


Miglustat is an oral medication for treatment of lysosomal storage diseases such as Gaucher disease type I and Niemann Pick disease type C. In many cases application of Miglustat is associated with symptoms similar to those observed in intestinal carbohydrate malabsorption. Previously, we have demonstrated that intestinal disaccharidases are inhibited immediately by Miglustat in the intestinal lumen. Nevertheless, the multiple functions of Miglustat hypothesize long term effects of Miglustat on intracellular mechanisms, including glycosylation, maturation and trafficking of the intestinal disaccharidases. Our data show that a major long term effect of Miglustat is its interference with N-glycosylation of the proteins in the ER leading to a delay in the trafficking of sucrase-isomaltase. Also association with lipid rafts and plausibly apical targeting of this protein is partly affected in the presence of Miglustat. More drastic is the effect of Miglustat on lactase-phlorizin hydrolase which is partially blocked intracellularly. The de novo synthesized SI and LPH in the presence of Miglustat show reduced functional efficiencies according to altered posttranslational processing of these proteins. However, at physiological concentrations of Miglustat (≤50 μM) a major part of the activity of these disaccharidases is found to be still preserved, which puts the charge of the observed carbohydrate maldigestion mostly on the direct inhibition of disaccharidases in the intestinal lumen by Miglustat as the immediate side effect.

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lactase-phlorizin hydrolase


brush border membrane


detergent-resistant membranes


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During the course of this work M.A. was a recipient of a Ph. D. scholarship from the German Academic Exchange Service (DAAD), Bonn, Germany. We would like to thank Actelion Pharmaceuticals GmbH, Freiburg, Germany for providing Miglustat for this study.

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Correspondence to Hassan Y. Naim.

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Communicated by: Matthias Baumgartner

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Amiri, M., Naim, H.Y. Long term differential consequences of miglustat therapy on intestinal disaccharidases. J Inherit Metab Dis 37, 929–937 (2014).

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