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

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1102-1107
Number of pages6
JournalGenetics in Medicine
Volume22
Issue number6
DOIs
StatePublished - Jun 1 2020

Keywords

  • Nijmegen Pediatric CDG Rating Scale (NPCRS)
  • SLC35A2-CDG
  • galactose
  • glycan
  • glycosylation

ASJC Scopus subject areas

  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Clinical and biochemical improvement with galactose supplementation in SLC35A2-CDG'. Together they form a unique fingerprint.

Cite this