D-galactose supplementation in individuals with PMM2-CDG: results of a multicenter, open label, prospective pilot clinical trial

Peter Witters, Hans Andersson, Jaak Jaeken, Laura Tseng, Clara D M van Karnebeek, Dirk J Lefeber, David Cassiman, Eva Morava, Peter Witters, Hans Andersson, Jaak Jaeken, Laura Tseng, Clara D M van Karnebeek, Dirk J Lefeber, David Cassiman, Eva Morava

Abstract

PMM2-CDG is the most prevalent congenital disorder of glycosylation (CDG) with only symptomatic therapy. Some CDG have been successfully treated with D-galactose. We performed an open-label pilot trial with D-galactose in 9 PMM2-CDG patients. Overall, there was no significant improvement but some milder patients did show positive clinical changes; also there was a trend toward improved glycosylation. Larger placebo-controlled studies are required to determine whether D-galactose could be used as supportive treatment in PMM2-CDG patients.Trial registration ClinicalTrials.gov Identifier: NCT02955264. Registered 4 November 2016, https://ichgcp.net/clinical-trials-registry/NCT02955264.

Keywords: Congenital disorder of glycosylation (CDG); D-galactose; Glycosylation; Nijmegen pediatric CDG rating scale (NPCRS); PMM2-CDG.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Response to Galactose treatment. Response to escalating dose of oral D-galactose supplementation in nine patients carrying different biallelic pathogenic variants in PMM2 on the NPCRS score (a)–(d) and on glycosylation (e), (f)

References

    1. Ferreira CR, Altassan R, Marques-Da-Silva D, Francisco R, Jaeken J, Morava E. Recognizable phenotypes in CDG. J Inherit Metab Dis. 2018;41:541–553. doi: 10.1007/s10545-018-0156-5.
    1. Witters P, Honzik T, Bauchart E, Altassan R, Pascreau T, Bruneel A, et al. Long-term follow-up in PMM2-CDG: are we ready to start treatment trials? Genet Med. 2018
    1. Altassan R, Péanne R, Jaeken J, Barone R, Bidet M, Borgel D, et al. International clinical guidelines for the management of phosphomannomutase 2-congenital disorders of glycosylation: diagnosis, treatment and follow up. J Inherit Metab Dis. 2019;42:5–28. doi: 10.1002/jimd.12024.
    1. Witters P, Cassiman D, Morava E. Nutritional therapies in congenital disorders of glycosylation (CDG). Nutrients. 2017;9.
    1. Verheijen J, Tahata S, Kozicz T, Witters P, Morava E. Therapeutic approaches in congenital disorders of glycosylation (CDG) involving N-linked glycosylation: an update. Genet Med. 2020;22:268–279. doi: 10.1038/s41436-019-0647-2.
    1. Morelle W, Potelle S, Witters P, Wong S, Climer L, Lupashin V, et al. Galactose supplementation in patients With TMEM165-CDG rescues the glycosylation defects. J Clin Endocrinol Metab. 2017;102:1375–1386. doi: 10.1210/jc.2016-3443.
    1. Radenkovic S, Bird MJ, Emmerzaal TL, Wong SY, Felgueira C, Stiers KM, et al. The metabolic map into the pathomechanism and treatment of PGM1-CDG. Am J Hum Genet. 2019;104:835–846. doi: 10.1016/j.ajhg.2019.03.003.
    1. Wong SY-W, Gadomski T, van Scherpenzeel M, Honzik T, Hansikova H, Holmefjord KSB, et al. Oral D-galactose supplementation in PGM1-CDG. Genet Med. 2017;19:1226–35.
    1. Frustaci A, Chimenti C, Ricci R, Natale L, Russo MA, Pieroni M, et al. Improvement in cardiac function in the cardiac variant of Fabry’s disease with galactose-infusion therapy. N Engl J Med. 2001;345:25–32. doi: 10.1056/NEJM200107053450104.
    1. De Smet E, Rioux J-P, Ammann H, Déziel C, Quérin S. FSGS permeability factor-associated nephrotic syndrome: remission after oral galactose therapy. Nephrol Dial Transplant. 2009;24:2938–2940. doi: 10.1093/ndt/gfp278.
    1. van Scherpenzeel M, Steenbergen G, Morava E, Wevers RA, Lefeber DJ. High-resolution mass spectrometry glycoprofiling of intact transferrin for diagnosis and subtype identification in the congenital disorders of glycosylation. Transl Res. 2015;166(639–649):e1.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere