JIMD Reports (Jul 2021)

Translational balancing questioned: Unaltered glycosylation during disulfiram treatment in mannosyl‐oligosaccharide alpha‐1,2‐mannnosidase‐congenital disorders of glycosylation (MAN1B1‐CDG)

  • Lisa Kemme,
  • Marianne Grüneberg,
  • Janine Reunert,
  • Stephan Rust,
  • Julien Park,
  • Cordula Westermann,
  • Yoshinao Wada,
  • Oliver Schwartz,
  • Thorsten Marquardt

DOI
https://doi.org/10.1002/jmd2.12213
Journal volume & issue
Vol. 60, no. 1
pp. 42 – 55

Abstract

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Abstract MAN1B1‐CDG is a multisystem disorder caused by mutations in MAN1B1, encoding the endoplasmic reticulum mannosyl‐oligosaccharide alpha‐1,2‐mannnosidase. A defect leads to dysfunction within the degradation of misfolded glycoproteins. We present two additional patients with MAN1B1‐CDG and a resulting defect in endoplasmic reticulum‐associated protein degradation. One patient (P2) is carrying the previously undescribed p.E663K mutation. A therapeutic trial in patient 1 (P1) using disulfiram with the rationale to generate an attenuation of translation and thus a balanced, restored ER glycoprotein synthesis failed. No improvement of the transferrin glycosylation profile was seen.

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