Galactosemia, a single gene disorder with epigenetic consequences

Coman, David J., Murray, David W., Byrne, Jennifer C., Rudd, Pauline M., Bagadlia, Paola M., Doran, Peter D. and Treacy, Eileen P. (2010) Galactosemia, a single gene disorder with epigenetic consequences. Pediatric Research, 67 3: 286-292. doi:10.1203/PDR.0b013e3181cbd542

Author Coman, David J.
Murray, David W.
Byrne, Jennifer C.
Rudd, Pauline M.
Bagadlia, Paola M.
Doran, Peter D.
Treacy, Eileen P.
Title Galactosemia, a single gene disorder with epigenetic consequences
Journal name Pediatric Research   Check publisher's open access policy
ISSN 0031-3998
Publication date 2010-03-01
Sub-type Article (original research)
DOI 10.1203/PDR.0b013e3181cbd542
Open Access Status
Volume 67
Issue 3
Start page 286
End page 292
Total pages 7
Editor Sherin U Devaskar
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
Subject C1
920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified
110107 Metabolic Medicine
Abstract Long-term outcomes of classic galactosemia (GAL) remain disappointing. It is unclear if the complications result mainly from prenatal-neonatal toxicity or persistent glycoprotein and glycolipid synthesis abnormalities. We performed gene expression profiling (T transcriptome) to characterize key-altered genes and gene clusters of four patients with GAL with variable outcomes maintained on a galactose-restricted diet, compared with controls. Significant perturbations of multiple cell signaling pathways were observed including mitogen-activated protein kinase (MAPK) signaling, regulation of the actin cytoskeleton, focal adhesion, and ubiquitin mediated proteolysis. A number of genes significantly altered were further investigated in the GAL cohort including SPARC (osteonectin) and S100A8 (S100 calcium-binding protein). The whole serum N-glycan profile and IgG glycosylation status of 10 treated patients with GAL were compared with healthy control serum and IgG using a quantitative high-throughput analytical HPLC platform. Increased levels of agalactosylated and monogalactosylated structures and decreases in certain digalactosylated structures were identified in the patients. The persistent abnormal glycosylation of serum glycoproteins seen with the microarray data indicates persisting metabolic dyshomeostasis and gene dysregulation in “treated” GAL. Strict restriction of dietary galactose is clearly life saving in the neonatal period; long-term severe galactose restriction may contribute to ongoing systemic abnormalities.
Keyword long-term prognosis
Osteoclast Differentiation
Untreated galactosemia
Serum transferrin
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 30 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 28 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 14 Mar 2010, 10:01:14 EST