Missing Enzyme-Rescue Metabolite Causes Rare Skeletal Dysplasia
The study identifies TGDS as an enzyme producing UDP-4-keto-6-deoxyglucose, which reactivates UXS1, a key enzyme in glycosaminoglycan synthesis. Deficiency in TGDS impairs this process, leading to Catel–Manzke syndrome, a rare skeletal disorder, with evidence from cell models, patient fibroblasts, and mouse models supporting this molecular mechanism.