Effects of temporary low-dose galactose supplements in children aged 5–12 y with classical galactosemia: a pilot study

Abstract

Background: Classical galactosemia is caused by severe galactose-1-phosphate uridyltransferase deficiency. Despite life-long galactose-restriction, many patients experience long-term complications. Intoxication by galactose and its metabolites as well as over-restriction of galactose may contribute to the pathophysiology. We provided temporary low-dose galactose supplements to patients. We assessed tolerance and potential beneficial effects with clinical monitoring and measurement of biochemical, endocrine, and IgG N-glycosylation profiles. Methods: We enrolled 26 patients (8.6 ± 1.9 y). Thirteen were provided with 300 mg of galactose/day followed by 500 mg for 2 wk each (13 patient controls). results: We observed no clinical changes with the intervention. Temporary mild increase in galactose-1-phosphate occurred, but renal, liver, and bone biochemistry remained normal. Patients in the supplementation group had slightly higher leptin levels at the end of the study than controls. We identified six individuals as "responders" with an improved glycosylation pattern (decreased G0/G2 ratio, P < 0.05). There was a negative relationship between G0/G2 ratio and leptin receptor sOb-R in the supplementation group (P < 0.05). conclusion: Temporary low-dose galactose supplementation in children over 5 y is well tolerated in the clinical setting. It leads to changes in glycosylation in "responders". We consider IgG N-glycan monitoring to be useful for determining individual optimum galactose intake.

Classical Galactosaemia and CDG, the N-Glycosylation Interface. A Review

“…Also, while the severe restriction of dietary galactose in the affected newborn is life saving and largely reverses the N-glycan assembly defect, our studies suggest that over restriction of galactose in the long-term may contribute to ongoing N-glycan processing defects, evident in all the galactosaemia patients whom we have studied to date (Coman et al 2010;Coss et al 2012;Knerr et al 2015;Stockmann et al 2016).…”

“…We recently also published a study of 13 children with galactosaemia which indicated that a moderate increase in galactose intake may be well tolerated in children and may improve glycosylation (Knerr et al 2015).…”

“…Considering this variability in accessory pathways of galactose metabolism and linked glycosylation, we propose that the clinical outcomes observed in galactosaemia are multifactorial, influenced by prenatal toxicity and postnatal variation in accessory glycosylation pathways (Coss et al 2012;Knerr et al 2015).…”

Classical galactosaemia: novel insights in IgG N-glycosylation and N-glycan biosynthesis

“…28 We also demonstrated the presence of IgG N-glycan processing defects in adults and children with galactosaemia maintained on a galactose restricted diet using IgG galactose incorporation ratios. 19,20,28,29 We have also demonstrated modification of the defective glycosylation pathway with moderate galactose relaxation in a number of adults and children with galactosaemia, suggesting the presence of substantial variation in accessory glycosylation pathways in some patients, which may be modifiable with substrate (galactose exposure). 20,28,29 Our gene expression and protein findings suggest that there may also be a partial N-glycan assembly defect in treated adult patients that is at risk of being exacerbated during galactose intoxication.…”

IgG N-Glycosylation Galactose Incorporation Ratios for the Monitoring of Classical Galactosaemia

“…Of note, we have now reported this method in a moderate galactose relaxation dietary study in children (using galactose content of 300-500 mg/day). The method identified a number of favourable responders with improved glycosylation ratios with increasing galactose intake and an inverse relationship between the G0/G2 ratio and circulating leptin receptor (sOb-R) in the supplementation group (Knerr et al 2015).…”