Classical Galactosaemia is a rare disorder of carbohydrate metabolism caused by galactose-1-phosphate uridyltransferase (GALT) deficiency. It affects 1/16,000 births in the Irish population. 151 patients are currently treated at the Irish National Centre for Inherited Metabolic Disorders, 92% are homozygous for the severe Q188R GALT mutation. The disease is life-threatening in the neonate. The only treatment available is life-long galactose-restricted diet. Long-term complications however persist despite treatment including: developmental delay, cognitive impairment, speech abnormalities, ataxia, osteopenia and ovarian failure. In our earlier developmental work, we reported N-glycosylation glycoprotein abnormalities and developed a UPLC-HILIC test of galactose incorporation into IgG N-glycans as a monitoring biomarker. We also identified specific genes (e.g. Leptin, ALG9, ANXA1, SEPT4 and B4GALT1), that may act as biomarkers to monitor patients. We also identified corresponding low blood leptin levels in children and adults with Galactosaemia. In this application, we aim at translating our research into clinical practice with a view to improved monitoring and treatment outcomes.
Specific aims: 1) Translate the novel diagnostic tool of IgG N-glycan analysis into clinical practice. Recruit a larger cohort of Galactosaemia adolescents (≥12 years) and adults with various genotypes for IgG N-glycan analysis applied to monitoring and tailoring treatment. 2) Extend our studies of newly identified markers to patients to include leptin, the leptin receptor axis and gene markers (Leptin, ALG9, ANXA1, SEPT4 and B4GALT1), compared to known fertility/endocrine markers and clinical outcomes. 3) Perform detailed outcome studies using our Galactosaemia national database, which will now be expanded for the European Galactosaemia Network (EGN). This database covers standardised sets of outcome variables approved by our European EGN collaborators. This approach will allow us to collect comprehensive national and international outcome data and make recommendations for the follow-up and treatment of patients with Galactosaemia.
