| Authors |
Rubio-Gozalbo, M. E ; Haskovic, M ; Bosch, A. M ; Burnytė, Birutė ; 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 |
| Abstract [eng] |
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. |
