Clinical and biochemical improvement with galactose supplementation in SLC35A2-CDG.

Peter Witters, Shawn Tahata, Rita Barone, Katrin Õunap, Ramona Salvarinova, Sabine Grønborg, George Hoganson, Fernando Scaglia, Andrea Margaret Lewis, Mari Mori, Jolanta Sykut-Cegielska, Andrew Edmondson, Miao He, Eva Morava

Journal: Genetics in medicine : official journal of the American College of Medical Genetics 2021;22(6):1102-1107

PMID: 32103184

Abstract

PURPOSE

We studied galactose supplementation in SLC35A2-congenital disorder of glycosylation (SLC35A2-CDG), caused by monoallelic pathogenic variants in SLC35A2 (Xp11.23), encoding the endoplasmic reticulum (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 Nijmegen Pediatric CDG Rating Scale (NPCRS) score (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, which included postural control, response to stimuli, and 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/disialo, P = 0.012 and monosialo/disialo, P = 0.017) and increased levels of a fully galactosylated N-glycan (P = 0.05).

CONCLUSIONS

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.

Address: Department of Paediatrics and Metabolic Center, University Hospitals Leuven, Leuven, Belgium.; Department of Development and Regeneration, KU Leuven, Leuven, Belgium.; Department of Clinical Genomics, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.; Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.; Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.; Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.; Children's & Women's Health Centre of British Columbia, Vancouver, BC, Canada.; Center for Inherited Metabolic Diseases, Department of Pediatrics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.; Department of Pediatrics, University of Illinois, IL, Chicago, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.; Texas Children's Hospital, Houston, TX, USA.; Joint BCM-CUHK Center of Medical Genetics, Prince of Wales Hospital, Shatin, Hong Kong.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.; Genetic and Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Inborn Errors of Metabolism and Paediatrics, Institute of Mother and Child, Warsaw, Poland.; Department of Pediatrics, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Department of Paediatrics and Metabolic Center, University Hospitals Leuven, Leuven, Belgium. [email protected].; Department of Development and Regeneration, KU Leuven, Leuven, Belgium. [email protected].; Department of Clinical Genomics, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA. [email protected].
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