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Title
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The natural history of classic galactosemia : lessons from the GalNet registry
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Orphanet journal of rare diseases. - London
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Publication
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London
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2019
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ISSN
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1750-1172
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DOI
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10.1186/S13023-019-1047-Z
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Volume/pages
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14
(2019)
, 11 p.
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Article Reference
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86
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ISI
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000466906200001
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Pubmed ID
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31029175
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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