Rubio-Gozalbo, M. E.Haskovic, M.Bosch, A. M.Burnyte, B.Coelho, A. I.Cassiman, D.Couce Pico, María LuzDawson, 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.2020-04-062020-04-062019Rubio-Gozalbo, M.E., Haskovic, M., Bosch, A.M. et al. The natural history of classic galactosemia: lessons from the GalNet registry. Orphanet J Rare Dis 14, 86 (2019). https://doi.org/10.1186/s13023-019-1047-zhttp://hdl.handle.net/10347/21208Background: 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 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.eng© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedhttps://creativecommons.org/licenses/by/4.0/RegistryNatural historyGalactosemiaGALT deficiencyGalactosemia networkjournal article10.1186/s13023-019-1047-z1750-1172open access