# Galactose tolerance in adults with classical galactosaemia. Considering the gaps

## TL;DR

This study explores how adults with galactosemia tolerate varying levels of galactose in their diet and how this affects their blood markers.

## Contribution

The study introduces serum IgG N-glycan profiling as a potential personalized treatment approach for classical galactosaemia.

## Key findings

- RBC Gal-1-P levels increased significantly with higher galactose intake.
- IgG N-glycan profiles showed minor but measurable changes with increased galactose intake.
- Moderate galactose intake up to 500 mg/day was well tolerated in most CG adults.

## Abstract

Classical galactosaemia (CG, OMIM 230400) is a rare inborn error of metabolism caused by deficiency of galactose-1-phosphate uridylyltransferase. The available modality of treatment, a galactose-restricted diet, is effective in preventing life-threatening neonatal symptoms. However long-term complications including neurological, speech and fertility issues in females remain prevalent.

This retrospective review reports the experience of mild-moderate relaxation of dietary galactose intake over time in a cohort of 31 Irish CG adult patients with established RBC Gal-1-P, and novel IgG N-glycan analysis. Three groups were categorised based on the retrospective analysis of estimated dietary galactose intake: Group 1 (<200 mg/day), Group 2 (200–500 mg/day) and Group 3 (501-1000 mg/day). Dietary galactose intake was compared to matching RBC Gal-1-P levels and serum IgG N-glycan profiles (measured by HILIC-UPLC).

RBC Gal-1-P levels increased with increased galactose intake with statistically significant differences only between the lowest and highest galactose intake group (p < 0.05). Minor changes were seen in a number of IgG N-glycans in the highest galactose intake group with increases in core fucosylated monoantennary and biantennary monogalactosylated monosialylated glycans, pentamannosylated glycans, oligomannosylated glycans and monoantennary glycans with a decrease in grouped biantennary glycans. The most significant change noted was an increase in pentamannosylated glycans with increased dietary galactose intake.

Moderate relaxation of dietary galactose intake (up to 500 mg/day) may be well tolerated in the majority of CG adults. These data suggest that serum N-glycan profiling may provide an improved individualised ‘personalised medicine’ approach for treatment interventions for CG, considering individualised variation in glycosylation, including ‘glycosylation outliers’.