Coagulation abnormalities and vascular complications are common in PGM1-CDG

Area of Science:

• Biochemistry
• Genetics
• Hematology

Background:

• Phosphoglucomutase-1-congenital disorder of glycosylation (PGM1-CDG) is a rare genetic disorder affecting the PGM1 enzyme.
• Clinical features include muscle, cardiac, and growth issues, alongside liver and coagulation abnormalities.
• The extent and treatment of coagulation defects in PGM1-CDG remain poorly understood.

Purpose of the Study:

• To determine the incidence and evolution of coagulation abnormalities in PGM1-CDG patients.
• To investigate the relationship between coagulation issues and clinical events.
• To assess the efficacy of D-galactose (D-gal) supplementation in improving coagulation parameters.

Main Methods:

• Retrospective analysis of 73 PGM1-CDG patients with molecularly confirmed diagnoses.
• Collection of coagulation data (antithrombin, aPTT, PT, etc.) and clinical events.
• Evaluation of longitudinal data from the FCDGC Natural History Study for 16 additional patients.

Main Results:

• Coagulation abnormalities were reported in 67.4% of individuals with available data, most commonly antithrombin (AT) deficiency (mean 30.8%).
• Four patients experienced major thrombotic events.
• D-galactose treatment led to significant improvements in AT levels (mean 64.5%) and other parameters in treated patients.

Conclusions:

• Coagulation abnormalities are a frequent complication of PGM1-CDG.
• D-galactose supplementation demonstrates a beneficial effect on coagulation parameters in PGM1-CDG.
• Routine monitoring of coagulation parameters and AT levels as a clinical endpoint for trials is recommended.