title: Systemic gene dysregulation in classical Galactosaemia: Is there a central mechanism?
abstract: Classical Galactosaemia is a rare disorder of carbohydrate metabolism caused by a deficiency of galactose-1-phosphate uridyltransferase (GALT). The disease is life-threatening in the neonate, and the only treatment option is life-long dietary restriction of galactose. However, long-term complications persist in treated patients including cognitive impairments, speech and language abnormalities and premature ovarian insufficiency in females. Microarray analysis of T-lymphocytes from treated adult patients identified systemic dysregulation of numerous gene pathways, including the glycosylation, inflammatory and inositol pathways. Analysis of gene expression in patient-derived dermal fibroblasts of patients exposed to toxic levels of galactose, with immunostaining, has further identified the susceptibility of the glycosylation gene alpha-1,2-mannosyltransferase (ALG9) and the inflammatory gene annexin A1 (ANXA1) to increased galactose concentrations. These data suggest that Galactosaemia is a multi-system disorder affecting numerous signalling pathways.
authors.affiliation: University College Dublin, Clinical Research Centre, Mater Misericordiae University Hospital, Ireland.
authors.forename: K P
authors.initials: KP
authors.lastname: Coss
authors.affiliation: University College Dublin, Clinical Research Centre, Mater Misericordiae University Hospital, Ireland; National Centre for Inherited Metabolic Disorders, Ireland; Trinity College Dublin, Ireland. Electronic address: etreacy@mater.ie.
authors.forename: E P
authors.initials: EP
authors.lastname: Treacy
authors.affiliation: University College Dublin, Clinical Research Centre, Mater Misericordiae University Hospital, Ireland.
authors.forename: E J
authors.initials: EJ
authors.lastname: Cotter
authors.affiliation: National Centre for Inherited Metabolic Disorders, Ireland.
authors.forename: I
authors.initials: I
authors.lastname: Knerr
authors.affiliation: Royal College of Surgeons in Ireland, Department of Physiology and Medical Physics, Dublin 2, Ireland.
authors.forename: D W
authors.initials: DW
authors.lastname: Murray
authors.affiliation: University Children's Hospital and Molecular Genetics and Metabolism Laboratory, Munich, Germany.
authors.forename: Y S
authors.initials: YS
authors.lastname: Shin
authors.affiliation: University College Dublin, Clinical Research Centre, Mater Misericordiae University Hospital, Ireland. Electronic address: peter.doran@ucd.ie.
authors.forename: P P
authors.initials: PP
authors.lastname: Doran
mesh_terms: D000293:Adolescent; D000328:Adult; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D005260:Female; D005693:Galactosemias / Q000235:genetics* / Q000378:metabolism; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D008364:Mannosyltransferases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D013601:T-Lymphocytes / Q000378:metabolism; D059467:Transcriptome; D055815:Young Adult
chemical_list: D017305:Annexin A1; D008565:Membrane Proteins; C469962:ALG9 protein, human; D008364:Mannosyltransferases
keywords: Biomarkers; Galactosaemia; Genomics; Glycosylation; Inflammation