Clinical and biochemical improvement with galactose supplementation in SLC35A2-CDG
| Autor: | Mari Mori, Rita Barone, Katrin Õunap, Ramona Salvarinova, Fernando Scaglia, Eva Morava, Jolanta Sykut-Cegielska, Sabine Grønborg, Peter Witters, Miao He, Andrew C. Edmondson, Andrea M. Lewis, Shawn Tahata, George E. Hoganson |
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| Rok vydání: | 2020 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities medicine.medical_specialty Glycosylation glycosylation galactose Nijmegen Pediatric CDG Rating Scale (NCPRS) Gastroenterology Article Postural control chemistry.chemical_compound symbols.namesake Epilepsy Congenital Disorders of Glycosylation Swallowing Internal medicine SLC35A2-CDG medicine Humans Dietary therapy Child Genetics (clinical) glycan business.industry Epileptic encephalopathy Golgi apparatus medicine.disease chemistry Galactose Dietary Supplements symbols Nijmegen Pediatric CDG Rating Scale (NPCRS) business |
| Zdroj: | Genetics in medicine : official journal of the American College of Medical Genetics |
| ISSN: | 1098-3600 |
| Popis: | 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. 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). 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). 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. |
| Databáze: | OpenAIRE |
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