Abstract Details

To determine  electrodiagnostic patterns associated with different gene mutation in patients with congenital disorders of glycosylation (CDG)

CDG’s are a group of inherited genetic defects involved in the synthesis and attachment of glycans on to proteins or lipids that affects multiple organ systems. PMM2-CDG (formerly CDG-1a) is the most common defect in this group though more than 150 CDG disorders have now been identified. Peripheral nervous system (PNS) involvement is varied and  may manifest as a neuropathy, myopathy or  myasthenic syndrome depending on the gene defect.  

Patients were enrolled in protocol “Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation” (NCT02089789) for prospective evaluations including standard electrodiagnostic studies that included nerve conduction studies (NCS) and needle EMG.  Peripheral sympathetic function was also evaluated by a Quantitative Sudomotor Axon Reflex Test (QSART).  

A total of 60 patients with CDG underwent electrodiagnostic testing with 93% (n=56) having electrodiagnostic abnormalities; 71% (n=52) had neuropathy and 29% (n=4) had a primary muscle disorder.   The most common disorders  in this study were PMM2-CDG (n=14) and the only de-glycosylation disorders identified to date NGLY1-CDDG (n=14) with the remainder of the disorders having 1-2 patients.  PMM2-CDG commonly presented as a demyelinating neuropathy.  NGLY1-CDDG presented as a severe sensorimotor axonal neuropathy with demyelinative component and was associated with anhidrosis.  Sensorimotor or pure sensory neuropathies were associated with ARV1-CDG, ALG1-CDG, GET4-CDG, CAD-CDG, PIGA-CDG, PIGN-CDG and ALG13-CDG gene defects. Primary muscle disorders were associated with PIGT-CDG, ALG6-CDG, and SCL34A2-CDG disorders.  Myasthenic syndromes were not observed in this population though only limited number of repetitive nerve studies were performed.

Our study provides  further  understanding of the PNS pathophysiology in  this rare  group of genetic disorders.  Electrodiagnostic studies could be a useful longitudinal measure in natural history or treatment studies in CDG populations.