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

Additional Metadata
Keywords Registry, Natural history, Galactosemia, GALT deficiency, Galactosemia network
Persistent URL dx.doi.org/10.1186/s13023-019-1047-z, hdl.handle.net/1765/116995
Journal Orphanet Journal of Rare Diseases
Citation
Rubio-Gozalbo, M.E, Haskovic, M., van den Bosch, A.M., Burnyte, B., Coelho, A.I., Cassiman, D, … Berry, G.T. (2019). The natural history of classic galactosemia: lessons from the GalNet registry. Orphanet Journal of Rare Diseases, 14. doi:10.1186/s13023-019-1047-z