New Eng J Med paper on a new treatable Glycosylation Disorder

Lefeber Dirk

Research from a large international team, led by Dirk Lefeber, Dept. of Neurology, Radboudumc and Thorsten Marquardt (Munster), has revealed novel insights in an exercise induced muscle disease that formed the basis for succesful treatment in patients.

Only a single adult patient had been described thus far with isolated muscle disease, caused by deficiency of phosphoglucomutase (PGM1), a key enzyme in energy metabolism. In Nijmegen, we have combined whole exome sequencing with detailed glycoprofiling of intact proteins using high-resolution nanochip QTOF mass spectrometry. This revealed not only a novel link between energy metabolism and protein glycosylation via PGM1, but also directly resulted in a unique biomarker for this disease, and identification of 20 patients via a simple blood test. The phenotype was extensive with young children suffering from hypoglycemia, liver failure, heart and muscle problems. Some patients died of heart failure. Further research revealed mechanistic insights in disease pathology, which allowed successful dietary intervention in  patients. In a bloodspot assay, PGM1 deficiency could be clearly distinguished from 3000 controls, allowing future inclusion in neonatal screening programs to initiate early intervention before disease symptoms occur. 

New Eng J Med Paper: link

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