Efficacy of oral manganese and D-galactose therapy in a patient bearing a novel TMEM165 variant

TMEM165-CDG has first been reported in 2012 and manganese supplementation was shown highly efficient in rescuing glycosylation in isogenic KO cells. The unreported homozygous missense c.928G>C; p.Ala310Pro variant leading to a functional but unstable protein was identified. This patient was diagn...

Full description

Saved in:
Bibliographic Details
Published in:Translational research : the journal of laboratory and clinical medicine 2024-04, Vol.266, p.57-67
Main Authors: Durin, Zoé, Raynor, Alexandre, Fenaille, François, Cholet, Sophie, Vuillaumier-Barrot, Sandrine, Alili, Jean-Meidi, Poupon, Joël, Oussedik, Nouzha Djebrani, Tuchmann-Durand, Caroline, Attali, Jennifer, Touzé, Romain, Dupré, Thierry, Lebredonchel, Elodie, Akaffou, Marlyse Angah, Legrand, Dominique, de Lonlay, Pascale, Bruneel, Arnaud, Foulquier, François
Format: Article
Language:English
Subjects:
galactose
Glycosylation
Golgi
Life Sciences
Manganese
TMEM165
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:TMEM165-CDG has first been reported in 2012 and manganese supplementation was shown highly efficient in rescuing glycosylation in isogenic KO cells. The unreported homozygous missense c.928G>C; p.Ala310Pro variant leading to a functional but unstable protein was identified. This patient was diagnosed at 2 months and displays a predominant bone phenotype and combined defects in N-, O- and GAG glycosylation. We administered for the first time a combined D-Gal and Mn2+ therapy to the patient. This fully suppressed the N-; O- and GAG hypoglycosylation. There was also striking improvement in biochemical parameters and in gastrointestinal symptoms. This study offers exciting therapeutic perspectives for TMEM165-CDG.
ISSN:1931-5244
1878-1810
DOI:10.1016/j.trsl.2023.11.005