The natural history of classic galactosemia: Lessons from the GalNet registry
Rubio-Gozalbo, M. E.; Haskovic, M.; Bosch, A. M.; Burnyte, B.; Coelho, A. I.; Cassiman, D.; Couce, M. L.; Dawson, C.; Demirbas, D.; Derks, T.; Eyskens, F.; Forga, M. T.; Grunewald, S.; Häberle, J.; Hochuli, M.; Hubert, A.; Huidekoper, H. H.; Janeiro, P.; Kotzka, J.; Knerr, I.; Labrune, P.; Landau, Y. E.; Langendonk, J. G.; Möslinger, D.; Müller-Wieland, D.; Murphy, E.; Õunap, K.; Ramadza, D.; Rivera, I. A.; Scholl-Buergi, S.; Stepien, K. M.; Thijs, A.; Tran, C.; Vara, R.; Visser, G.; Vos, R.; De Vries, M.; Waisbren, S. E.; Welsink-Karssies, M. M.; Wortmann, S. B.; Gautschi, M.; Treacy, E. P.; Berry, G. T.
(2019) Orphanet Journal of Rare Diseases, volume 14, issue 1
(Article)
Abstract
Background: Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome
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complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients. Methods: Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018. Results: Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome. Conclusion: This study describes the natural history of classic galactosemia based on the hitherto largest data set.
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Keywords: GALT deficiency, Galactosemia, Galactosemia network, Natural history, Registry
ISSN: 1750-1172
Publisher: BioMed Central
Note: Funding Information: M.E.R-G., M.H., B.B., A.I.C., D.C, M.L.C., C.D., D.D., T.D., F.E., M.T.F., S.G., J.H., M.H., A.H., H.H.H., P.J., J.K., I.K., P.L., Y.E.L., J.G.L., D.M., D.M-W., K.Õ., D.R., I.A.R., S.S-B., K.M.S., A.T., C.T., R.Va., G.V., R.Vo., M.V., S.E.W., M.W-K., S.B.W., M.G., E.P.T., G.T.B. declare that they have no competing interests. A.M.B. has received a speakers fee and has been a member of advisory boards for Nutricia and Biomarin. E.M. has received travel funding, research grants and support from Nutricia UK. Funding Information: The initial GalNet meeting to discuss the registry was financially supported by a grant to M.E.R-G. from The Netherlands Organisation for Scientific Research (NWO). Development, implementation and maintenance were supported by grants from the Dutch Galactosemia Research foundation, European Galactosemia Society and Metakids grants to M.E. R-G. Data entry for 6 of the 7 participating Dutch centers was done by the coordinating center and was financially supported by a Stofwisselkracht grant to M.E.R-G. in 2016. Analysis and interpretation of data was financially supported by Stofwisselkracht and Metakids grants to M.E.R-G. (2017 and 2018). The Irish data entry was supported by a national Health Research Board (HRB) grant to E.P.T. The British inherited Metabolic Disease Group supported access to the registry in the UK. M.G. was supported by a grant from the Batzebär foundation of the University Hospital Bern, and one from the Galaktosämie Schweiz patient organization for the set-up of the registry and data entry for all patients of Switzerland. The Spanish Galactosemia foundation financially supported data entry for Spanish patients. Publisher Copyright: © 2019 The Author(s).
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