Naslov
The natural history of classic galactosemia: lessons from the GalNet registry

Autori
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. ; Ramadža, Danijela ; 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.

Kolaboracija
The galactosemia network (GalNet)

Izvornik
Orphanet Journal of Rare Diseases (1750-1172) 14 (2019), 1; 86, 11

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Registry, Natural history, Galactosemia, GALT deficiency, Galactosemia network

Sažetak
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 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.

Izvorni jezik
Engleski

POVEZANOST RADA