@article{3471cd51a69948d3a5d886b98757e12b,
title = "The natural history of classic galactosemia: lessons from the GalNet registry",
abstract = "BackgroundClassic 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.MethodsObservational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018.ResultsMost 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.ConclusionThis study describes the natural history of classic galactosemia based on the hitherto largest data set.",
keywords = "Registry, Natural history, Galactosemia, GALT deficiency, Galactosemia network, ADULT PATIENTS, VITAMIN-D, COMPLICATIONS, RESTRICTION, PREVALENCE, METABOLISM, CHILDREN, OUTCOMES, DENSITY, HEALTH",
author = "Rubio-Gozalbo, {M. E.} and M. Haskovic and Bosch, {A. M.} and B. Burnyte and Coelho, {A. I.} and D. Cassiman and Couce, {M. L.} and C. Dawson and D. Demirbas and T. Derks and F. Eyskens and Forga, {M. T.} and S. Grunewald and J. Haberle and M. Hochuli and A. Hubert and Huidekoper, {H. H.} and P. Janeiro and J. Kotzka and I. Knerr and P. Labrune and Landau, {Y. E.} and Langendonk, {J. G.} and D. Moeslinger and D. Mueller-Wieland and E. Murphy and K. Ounap and D. Ramadza and Rivera, {I. A.} and S. Scholl-Buergi and Stepien, {K. M.} and A. Thijs and C. Tran and R. Vara and G. Visser and R. Vos and {de Vries}, M. and Waisbren, {S. E.} and Welsink-Karssies, {M. M.} and Wortmann, {S. B.} and M. Gautschi and Treacy, {E. P.} and Berry, {G. T.}",
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.{\~O}., 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 Batzeb{\"a}r foundation of the University Hospital Bern, and one from the Galaktos{\"a}mie 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: {\textcopyright} 2019 The Author(s).",
year = "2019",
month = apr,
day = "27",
doi = "10.1186/s13023-019-1047-z",
language = "English",
volume = "14",
journal = "Orphanet Journal of Rare Diseases",
issn = "1750-1172",
publisher = "BioMed Central Ltd",
}