@article{968bad897faf4b4aa8b211e30e293aeb,
title = "Galactokinase deficiency: lessons from the GalNet registry",
abstract = "Purpose Galactokinase (GALK1) deficiency is a rare hereditary galactose metabolism disorder. Beyond cataract, the phenotypic spectrum is questionable. Data from affected patients included in the Galactosemias Network registry were collected to better characterize the phenotype. Methods Observational study collecting medical data of 53 not previously reported GALK1 deficient patients from 17 centers in 11 countries from December 2014 to April 2020. Results Neonatal or childhood cataract was reported in 15 and 4 patients respectively. The occurrence of neonatal hypoglycemia and infection were comparable with the general population, whereas bleeding diathesis (8.1% versus 2.17-5.9%) and encephalopathy (3.9% versus 0.3%) were reported more often. Elevated transaminases were seen in 25.5%. Cognitive delay was reported in 5 patients. Urinary galactitol was elevated in all patients at diagnosis; five showed unexpected Gal-1-P increase. Most patients showed enzyme activities A (p.Pro28Thr). Thirty-five patients were diagnosed following newborn screening, which was clearly beneficial. Conclusion The phenotype of GALK1 deficiency may include neonatal elevation of transaminases, bleeding diathesis, and encephalopathy in addition to cataract. Potential complications beyond the neonatal period are not systematically surveyed and a better delineation is needed.",
keywords = "galactokinase 1 deficiency, cataract, galactosemias registry, GALK1gene variants, neonatal complications, GALACTOSEMIA, ERYTHROCYTES, MUTATION, VARIANT",
author = "Rubio-Gozalbo, {M. Estela} and Britt Derks and Das, {Anibh Martin} and Uta Meyer and Dorothea Moeslinger and Couce, {M. Luz} and Aurelie Empain and Can Ficicioglu and Palacios, {Natalia Julia} and {De Los Santos De Pelegrin}, {Mariela M.} and Rivera, {Isabel A.} and Sabine Scholl-Buergi and Bosch, {Annet M.} and David Cassiman and Didem Demirbas and Matthias Gautschi and Ina Knerr and Philippe Labrune and Anastasia Skouma and Patrick Verloo and Wortmann, {Saskia B.} and Treacy, {Eileen P.} and Timson, {David J.} and Berry, {Gerard T.}",
note = "Funding Information: We thank E. Crushell, C. De Laet, A. Nuoffer, and N. Vanhoutvin for their help in entering data in the GalNet registry. We thank R. Vos for his help in the statistical analysis. We thank R. Dalgleish for his help in validating the descriptions of the DNA variants. This work was financially supported by several foundations. A grant from The Netherlands Organisation for Scientific Research (NOW) to M.E.R.-G. financed the GalNet meeting to discuss the registry. The Dutch Galactosemia Research foundation, European Galactosemia Society and Metakids grants to M.E.R.-G. financially supported the development, implementation, maintenance, and analysis of the GalNet registry. The coordinating center did the data entry of all galactosemia patients for 6 of the 7 participating Dutch centers and was financially supported by a Stofwisselkracht grant to M.E.R.-G. Stofwisselkracht and Metakids grant to M.E.R.-G. financially supported the analysis and interpretation of the data. A national Health Research Board (HRB) grant to E.P.T. financed the development of the registry in Ireland. Data entry for the patients from Switzerland was financially supported by a grand from the Batzeb{\"a}r foundation of the University Hospital Bern to M.G. and by the Galactos{\"a}mie Schweiz patient organization. Data entry for the patients from Spain was financed by the Spanish Galactosemia foundation. eCRFs development for data entry: M.E.R.-G., A.M.B., E.P.T., M.G., G.T.B. Implementation and Coordination of registry: M.E.R.-G. Financial support grant writing for design, implementation, maintenance of the registry: M.E.R.-G. Those responsible for obtaining ethical approval at the different centers, informed consent from patients, collecting medical data and entry of the data: M.E.R.-G., B.D., A.M.D., U.M., D.M., M.L.C., A.E., C.F., N.J.P., M.M.L.S.-P., I.A.R., S.S.B., A.M.B., D.C., D.D., M.G., I.K., P.L., A.S., P.V., S.B.W., E.P.T., D.J.T., G.T.B.. Curation of data: M.E.R.-G. Data analysis and interpretation: M.E.R.-G., B.D. Manuscript writing: M.E.R.-G., B.D., D.D., D.J.T., G.T.B. Manuscript editing and final approval: all authors. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2021",
month = jan,
doi = "10.1038/s41436-020-00942-9",
language = "English",
volume = "23",
pages = "202--210",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Nature Publishing Group",
number = "1",
}