Dietary intervention has been a successful approach of treatment in classic inborn errors, aiming at restoring normal levels of metabolites in patients. In the past, a positive effect of the monosaccharide, D-galactose has been documented in Golgi related CDG. Our preliminary data in PGM1-CDG and SLC35A2-CDG showed that supplementation of patients with D-galactose leads to improvement of glycan synthesis parallel with improving clinical symptoms. In another glycosylation disorder, NGLY1 deficiency, preclinical studies offered a different therapeutic target for the disease. Despite these encouraging preliminary observations we do need clinical trials to 1) evaluate long-term therapy, dosage and safety of oral D-galactose supplementation in patients with PGM1-CDG; 2) study the efficacy of oral D-galactose supplementation in patients with another protein- galactosylation defect (SLC35A2-CDG) and 3) evaluate whether oral GlcNAc supplementation in NGLY1 deficiency is translatable to the human disorder. Our scientific premise is that the use dietary sugars, D- galactose and N-Acetyl-Glucosamine will restore glycosylation in CDG by influencing ?metabolite fluxes? to regulate and boost glycosylation pathways leading to improved clinical symptoms and quality of life of CDG patients. We propose to 1) evaluate efficacy and safety of D-galactose supplementation in SLC35A2-CDG, a disorder of hypogalactosylation, using seizure control, quantitative glycomics and validated clinical severity score (NPCRS) as endpoints in a blinded, cross-over study design; 2) assess optimal dosing and long-term safety of D-galactose in PGM1- CDG using validated clinical severity score (TPCRS) and quantitative glycomics as endpoints in an open label dose escalation study design and 3) evaluate the safety and effect of oral GlcNAc supplementation in patients with NGLY1 deficiency on a novel urinary biomarker, seizure control and tear secretion, as end points. The proposed clinical trials will fill gaps in the design of upcoming clinical trials in CDG and NGLY1 by establishing initial treatment regimens and clarifying safe dosage for monosaccharide therapies. Deliverables from this study, supported by the natural history study and the diagnostics and biomarker project will increase clinical trial readiness for large-scale Phase 2 and Phase 3 clinical trials by validating clinical progression scores and patient reported outcomes (Goal Attainment Scale) as well as advanced diagnostics and biomarker discoveries.