Header

UZH-Logo

Maintenance Infos

The natural history of classic galactosemia: lessons from the GalNet registry


Rubio-Gozalbo, M E; Haskovic, M; et al; Häberle, J; Hochuli, M; Tran, C; Gautschi, M (2019). The natural history of classic galactosemia: lessons from the GalNet registry. Orphanet Journal of Rare Diseases, 14(1):86.

Abstract

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.

Abstract

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.

Statistics

Citations

Dimensions.ai Metrics
26 citations in Web of Science®
23 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

19 downloads since deposited on 05 Jul 2019
8 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Genetics (clinical)
Health Sciences > Pharmacology (medical)
Language:English
Date:27 April 2019
Deposited On:05 Jul 2019 14:02
Last Modified:15 Apr 2020 23:50
Publisher:BioMed Central
ISSN:1750-1172
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s13023-019-1047-z
PubMed ID:31029175

Download

Gold Open Access

Download PDF  'The natural history of classic galactosemia: lessons from the GalNet registry'.
Preview
Content: Published Version
Filetype: PDF
Size: 859kB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)