NIH Research Festival
Background: Congenital Disorders of Glycosylation (CDG) are a group of rare genetic disorders, including 130 subtypes, that involve defects of the glycosylation pathway. The most common subtype is PMM2-CDG (formerly CDG1a) is autosomal recessive and multisystemic, with over 800 people diagnosed worldwide. NGLY1-CDG is autosomal recessive and is the first known congenital disorder of deglycosylation (CDDG) with approximately 66 patients diagnosed world-wide. There have been very few natural history studies reporting neurodevelopmental sequalae. Methods: Data were drawn from the CDG natural history protocol at NIH. Participants (n = 24) were enrolled between 0-33 years of age from two CDG Cohorts: PMM2-CDG (n = 10) and NGLY1-CDDG (n = 14). Specifiers for Intellectual Disability (ID) were measured using the Vineland Adaptive Behavior Scales, 2nd edition(VABs), and developmental and cognitive assessments. Results: NGLY1-CDDG participants (age 5 months to 21 years) had varied IQ's, but were predominantly diagnosed with ID in the profound and severe range. PMM2-CDG participants (age 2 years to 22 years) were predominantly diagnosed with ID, ranging from the mild to severe range. The mean standard scores of the domain and overall adaptive behavior composite score were lower in NGLY1-CDDG participants than PMM2-CDG participants. Detailed scores will be provided. Discussion: These findings suggest that although both PMM2-CDG and NGLY1-CDDG are associated with intellectual disability, NGLY1-CDDG patients are more impaired, there is variability in adaptive functioning across and within the two CDG subtypes. Further consideration should be given to longitudinal follow-up to understand the trajectory of skill development as children with these disorders grow.
Scientific Focus Area: Genetics and Genomics
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