Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun;22(6):1102-1107.
doi: 10.1038/s41436-020-0767-8. Epub 2020 Feb 27.

Clinical and biochemical improvement with galactose supplementation in SLC35A2-CDG

Peter Witters  1   2 , Shawn Tahata  3 , Rita Barone  4 , Katrin Õunap  5   6 , Ramona Salvarinova  7 , Sabine Grønborg  8 , George Hoganson  9 , Fernando Scaglia  10   11   12 , Andrea Margaret Lewis  10 , Mari Mori  13 , Jolanta Sykut-Cegielska  14 , Andrew Edmondson #  15 , Miao He #  16 , Eva Morava #  17   18   19
Affiliations

Clinical and biochemical improvement with galactose supplementation in SLC35A2-CDG

Peter Witters et al. Genet Med. 2020 Jun.

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.

Keywords: Nijmegen Pediatric CDG Rating Scale (NPCRS); SLC35A2-CDG; galactose; glycan; glycosylation.

PubMed Disclaimer

Conflict of interest statement

Conflict of interests

There are no conflicts of interests for any of the authors.

Figures

Figure 1
Figure 1
a Total score in Nijmegen pediatric CDG rating scale (before and after galactose supplementation) Mean total NPCRS score improved from 28.7 ± 9.7 to 24.6 ± 9.6 (P = 0.008) b System specific involvement in NCPRS (before and after galactose supplementation) System specific involvement improved from 5.1 ± 2.7 to 3.6 ± 2.6 (P = 0.042) c Current clinical assessment in NCPRS (before and after galactose supplementation) Current clinical assessment improved from 12.1 ± 3.8 to 10.2 ± 3.7 (P = 0.007)
Figure 2
Figure 2. Glycomics before and after galactose supplementation
a: A decrease in the mono-Gal/Di sialo upon treatment from 0.74 ± 1.27 to 0.45 ± 0.68 (p=0.011) b: A decrease in mono-sialic/disialic upon treatment from 0.51 ± 0.1 to 0.42 ± 0.09 (p=0.017)
See this image and copyright information in PMC

References

    1. Kodera H, Nakamura K, Osaka H, et al. De novo mutations in SLC35A2 encoding a UDP-galactose transporter cause early-onset epileptic encephalopathy. Hum Mutat. 2013;34:1708–1714. - PubMed
    1. Ng BG, Buckingham KJ, Raymond K, et al. Mosaicism of the UDP-galactose transporter SLC35A2 causes a congenital disorder of glycosylation. Am J Hum Genet. 2013;92:632–636. - PMC - PubMed
    1. Ng BG, Sosicka P, Agadi S, et al. SLC35A2-CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals. Hum Mutat. 2019;40:908–925. - PMC - PubMed
    1. Dörre K, Olczak M, Wada Y, et al. A new case of UDP-galactose transporter deficiency (SLC35A2-CDG): molecular basis, clinical phenotype, and therapeutic approach. J Inherit Metab Dis. 2015;38:931–940. - PubMed
    1. Kimizu T, Takahashi Y, Oboshi T, et al. A case of early onset epileptic encephalopathy with de novo mutation in SLC35A2: Clinical features and treatment for epilepsy. Brain Dev. 2017;39:256–260. - PubMed

Publication types