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
Affiliations
Lisa Kemme
University Children's Hospital Münster Muenster Germany
Marianne Grüneberg
University Children's Hospital Münster Muenster Germany
Janine Reunert
University Children's Hospital Münster Muenster Germany
Stephan Rust
University Children's Hospital Münster Muenster Germany
Julien Park
University Children's Hospital Münster Muenster Germany
Cordula Westermann
Gerhard‐Domagk‐Institute of Pathology University Hospital Muenster Muenster Germany
Yoshinao Wada
Osaka Medical Center and Research Institute for Maternal and Child Health Osaka Japan
Oliver Schwartz
University Children's Hospital Münster Muenster Germany
Thorsten Marquardt
University Children's Hospital Münster Muenster Germany
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.
