New technique to aid diagnosis of glycosylation disorders present at birth

A study, supported by the NIHR Great Ormond Street BRC, investigated the use of a 2D-differential gel electrophoresis (DIGE) method that provides a global analysis of the serum glycoproteome (glycomic profiling). 2D-DIGE allows multiple samples to be run simultaneously, eliminating gel-to-gel variations, and allowing direct overlay comparisons.

The results showed that for some CDG patients not all glycoproteins were consistently affected. The results identified several new and specific markers of N- and O-linked glycoproteins, never before described. These proteins were shown to be changed in patients, something that conventional tests failed to identify. The findings showed that 2D DIGE is an ideal method for investigation of the global glycoproteome and it could aid diagnosis and sub classification of complex CDG cases, with the potential to identify new diseases. This work was supported by the NIHR GOSH BRC and findings have been published in Molecular Genetics and Metabolism reports.

Congenital disorders of glycosylation (CDG) are a group of rare genetic, metabolic disorders caused by an error in glycosylation. There are over 60 different CDG identified, resulting in a broad range of clinical symptoms, making initial clinical assessment challenging. Screening of CDG is currently based on the investigation of the glycoproteins transferrin and apolipoprotein CIII. However, this cannot diagnose all potential defects in the glycosylation pathway and overlooks new inborn errors of metabolism, resulting in more subtle defects being missed.