The natural history of classic galactosemia: lessons from the GalNet registry.
GALT deficiency
Galactosemia
Galactosemia network
Natural history
Registry
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
27 04 2019
27 04 2019
Historique:
received:
15
01
2019
accepted:
12
03
2019
entrez:
29
4
2019
pubmed:
29
4
2019
medline:
26
11
2019
Statut:
epublish
Résumé
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. Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018. 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. This study describes the natural history of classic galactosemia based on the hitherto largest data set.
Sections du résumé
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.
Identifiants
pubmed: 31029175
doi: 10.1186/s13023-019-1047-z
pii: 10.1186/s13023-019-1047-z
pmc: PMC6486996
doi:
Substances chimiques
UTP-Hexose-1-Phosphate Uridylyltransferase
EC 2.7.7.10
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
86Subventions
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek
ID : -
Pays : International
Organisme : Dutch Galactosemia Research foundation
ID : -
Pays : International
Organisme : European Galactosemia Society
ID : -
Pays : International
Organisme : Metakids
ID : -
Pays : International
Organisme : Stofwisselkracht
ID : -
Pays : International
Organisme : Health Research Board
ID : -
Pays : Ireland
Organisme : British inherited Metabolic Disease Group
ID : -
Pays : International
Organisme : Batzebar foundation
ID : -
Pays : International
Organisme : Galaktosamie Schweiz patient organization
ID : -
Pays : International
Organisme : Spanish Galactosemia foundation
ID : -
Pays : International
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