Longitudinal analysis of clinical and biochemical outcomes during seven years of galactose supplementation in a patient with SLC35A2-CDG.
- 1Palmieri Metabolic Disease Laboratory, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
- 2Department of Pediatrics, Peking University People's Hospital, Beijing 100044, China.
- 3Department of Pediatrics, Division of Genetics and Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Abstract
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.
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BibTeX
@article{liu2026longitudinal,
title = {{Longitudinal analysis of clinical and biochemical outcomes during seven years of galactose supplementation in a patient with SLC35A2-CDG.}},
author = {Yupeng Liu and Earnest J P Daniel and Wenyue Zhang and Andrew Edmondson and Miao He},
journal = {Molecular genetics and metabolism reports},
year = {2026},
month = oct,
doi = {10.1016/j.ymgmr.2026.101375},
url = {https://europepmc.org/article/MED/42927181},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Longitudinal analysis of clinical and biochemical outcomes during seven years of galactose supplementation in a patient with SLC35A2-CDG.
AU - Yupeng Liu
AU - Earnest J P Daniel
AU - Wenyue Zhang
AU - Andrew Edmondson
AU - Miao He
PY - 2026
DA - 2026/10/16
JO - Molecular genetics and metabolism reports
DO - 10.1016/j.ymgmr.2026.101375
UR - https://europepmc.org/article/MED/42927181
AB - 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.
SN - 2214-4269
ER -