Congenital Disorders of Glycosylation in Portugal—Two Decades of Experience

Objective To describe the clinical, biochemical, and genetic features of both new previously reported patients with congenital disorders glycosylation (CDGs) diagnosed in Portugal over last 20 years. Study design The cohort includes an unexplained multisystem or single organ involvement, without psychomotor disability. Serum sialotransferrin isoforms and, whenever necessary, apolipoprotein CIII glycan structures were analyzed. Additional studies included measurement phosphomannomutase (PMM) activity analysis lipid-linked oligosaccharides fibroblasts. Sanger sequencing massive parallel used to identify causal variants affected gene, respectively. Results Sixty-three individuals covering 14 distinct CDGs; 43 postnatally revealed a type 1, 2, 2 normal pattern on serum transferrin isoelectrofocusing. latter identified by whole exome sequencing. Nine them presented also hypoglycosylation isoelectrofocusing, pointing associated O-glycosylation defect. Most (62%) are PMM2-CDG remaining carry pathogenic ALG1, ATP6AP1, ATP6AP2, ATP6V0A2, CCDC115, COG1, COG4, DPAGT1, MAN1B1, SLC35A2, SRD5A3, RFT1, PGM1. Conclusions Portuguese CDGs this report, some showing unique clinical phenotypes. Among genes mutated individuals, 8 shared Spanish cohort. However, regarding mutational spectrum PMM2-CDG, most frequent CDG, striking similarity between populations was found, as only 1 allele found group has not been Spain.