SLC37A4-CDG: Mislocalization of the glucose-6-phosphate transporter to the Golgi causes a new congenital disorder of glycosylation

Thorsten Marquardt; Vladimir Bzduch; Max Hogrebe; Stephan Rust; Janine Reunert; Marianne Grüneberg; Julien Park; Nico Callewaert; Robin Lachmann; Yoshinao Wada; Thomas Engel

doi:10.1016/j.ymgmr.2020.100636

SLC37A4-CDG: Mislocalization of the glucose-6-phosphate transporter to the Golgi causes a new congenital disorder of glycosylation

Mol Genet Metab Rep. 2020 Aug 21:25:100636. doi: 10.1016/j.ymgmr.2020.100636. eCollection 2020 Dec.

Authors

Affiliations

¹ University Children's Hospital Münster, Department of General Pediatrics, Münster, Germany.
² Comenius University, National Institute of Children's Diseases, Department of Paediatrics, Limbová 1, 83340 Bratislava, Slovakia.
³ Medical Biotechnology lab, Center for Medical Biotechnology, Technologiepark 71, B-9052 Gent-Zwijnaarde, Belgium.
⁴ Charles Dent Metabolic Unit Box 92, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.
⁵ Osaka Women's and Children's Hospital, Osaka, Japan.

Abstract

Loss-of-function of the glucose-6-phosphate transporter is caused by biallelic mutations in SLC37A4 and leads to glycogen storage disease Ib. Here we describe a second disease caused by a single dominant mutation in the same gene. The mutation abolishes the ER retention signal of the transporter and generates a weak Golgi retention signal. Intracellular mislocalization of the transporter leads to a congenital disorder of glycosylation instead of glycogen storage disease.

Keywords: CDG; Glycogen storage disease; Glycosylation; SLC37A4.