Longitudinal analysis of clinical and biochemical outcomes during seven years of galactose supplementation in a patient with SLC35A2-CDG

Background SLC35A2-CDG is a rare X-linked congenital disorder of glycosylation caused by impaired UDP-galactose transport into the Golgi apparatus, resulting in multisystem involvement with prominent neurological manifestations. Although oral galactose supplementation has been proposed as a targeted therapy, its long-term efficacy and safety remain unclear. Methods We report a longitudinal study of a female patient with SLC35A2-CDG treated with oral D-galactose supplementation over seven years. Clinical outcomes were assessed using the Nijmegen Pediatric CDG Rating Scale (NPCRS), and glycosylation abnormalities were monitored via N-glycomics profiling. Glycosylation biomarkers associated with clinical severity were subsequently applied retrospectively to evaluate eight additional SLC35A2-CDG patients with absent or uncertain responses to galactose therapy. Results Our index patient demonstrated significantly clinical and biochemical improvements, with the NPCRS score improving from 22 to 12. Plasma N-glycan profiling showed improvement and normalization in both under-galactosylated glycans and normally formed disialylated glycans. Fractionated N-glycan analysis confirmed consistent improvement in both affinity-purified transferrin and the triple-depleted plasma fraction with IgG, transferrin and albumin removed. Strong correlations were also identified between glycosylation markers and disease severity. In contrast, seven non-responder patients showed no obvious clinical or biochemical response, while one displayed partial biochemical improvement and steady clinical course. Conclusions This study provides the first long-term evidence that galactose supplementation is effective with meaningful clinical and biochemical improvement observed in a SLC35A2-CDG patient. Glycosylation profiling may serve as a supportive tool for monitoring treatment response and guiding individualized therapy.