Oral D-galactose supplementation in PGM1-CDG

Area of Science:

• Biochemistry
• Genetics
• Metabolic Disorders

Background:

• Phosphoglucomutase-1 deficiency (PGM1-CDG) is a rare genetic disorder affecting glycosylation.
• Previous case reports suggested oral D-galactose may benefit PGM1-CDG patients.
• Systematic studies on D-galactose safety and efficacy in PGM1-CDG were lacking.

Purpose of the Study:

• To prospectively evaluate the safety and efficacy of oral D-galactose supplementation in patients with PGM1-CDG.
• To monitor biochemical markers of glycosylation, coagulation, and organ function during D-galactose treatment.
• To investigate the in vitro effects of D-galactose on cellular glycosylation.

Main Methods:

• A prospective pilot study involving nine PGM1-CDG patients.
• Gradual dose escalation of oral D-galactose up to 1.5 g/kg/day over 18 weeks.
• Laboratory assessments of serum transferrin glycosylation, coagulation parameters, liver, and endocrine function; in vitro cellular glycosylation studies.

Main Results:

• Eight patients completed the study with no reported adverse effects.
• Significant improvements in transferrin glycosylation, antithrombin-III levels, and coagulation parameters were observed.
• In vitro studies demonstrated that D-galactose normalized various cellular glycosylation defects in PGM1-CDG fibroblasts.

Conclusions:

• Oral D-galactose supplementation is a safe and effective treatment for PGM1-CDG.
• Transferrin glycosylation and antithrombin-III levels serve as valuable endpoints for assessing treatment efficacy.
• Larger, longer-term clinical trials are warranted to further confirm these findings.