Clinical and biochemical improvement with galactose supplementation in SLC35A2-CDG

PURPOSE: We studied galactose supplementation in SLC35A2-congenital disorder of glycosylation (SLC35A2-CDG), caused by mono-allelic pathogenic variants in SLC35A2 (Xp11.23), encoding the ER and Golgi UDP-galactose transporter. Patients present with epileptic encephalopathy, developmental disability, growth deficiency, and dysmorphism. METHODS: Ten patients with SLC35A2-CDG were supplemented with oral D-galactose for 18 weeks in escalating doses up to 1.5 g/kg/day. Outcome was assessed using the Nijmegen Pediatric CDG Rating Scale (NPCRS, ten patients) and by glycomics (eight patients). RESULTS: SLC35A2-CDG patients demonstrated improvements in overall NPCRS (P=0.008), the current clinical assessment (P=0.007) and the system specific involvement (P=0.042) domains. Improvements were primarily in growth and development with five patients resuming developmental progress, that included postural control, response to stimuli, chewing and swallowing amelioration. Additionally, there were improvements in gastrointestinal symptoms and epilepsy. One patient in our study did not show any clinical improvement. Galactose supplementation improved patients’ glycosylation with decreased ratios of incompletely formed to fully formed glycans (M-gal/di-sialo, P=0.012 and mono-sialo/di-sialo, P=0.017) and increased levels of a fully galactosylated N-glycan (P=0.05). CONCLUSION: Oral D-galactose supplementation results in clinical and biochemical improvement in SLC35A2-CDG. Galactose supplementation may partially overcome the Golgi UDP-galactose deficiency and improves galactosylation. Oral galactose is well-tolerated and shows promise as dietary therapy.