biostudies-literatureBosnyak INational Institute of Neurological Disorders and StrokeNational Center for Advancing Translational SciencesNINDS NIH HHS135-143https://www.ebi.ac.uk/biostudies/studies/S-EPMC11078713biostudies-literatureUnknown65(3)ALG1-CDG is a rare, clinically variable metabolic disease, caused by the defect of adding the first mannose (Man) to N-acetylglucosamine (GlcNAc₂)-pyrophosphate (PP)-dolichol to the growing oligosaccharide chain, resulting in impaired N-glycosylation of proteins. N-glycosylation has a key role in functionality, stability, and half-life of most proteins. Therefore, congenital defects of glycosylation typically are multisystem disorders. Here we report a 3-year-old patient with severe neurological, cardiovascular, respiratory, musculoskeletal and gastrointestinal symptoms. ALG1-CDG was suggested based on exome sequencing and Western blot analysis. Despite her severe clinical manifestations and genetic diagnosis, serum transferrin glycoform analysis was normal. Western blot analysiJIMD reportsNormal transferrin glycosylation does not rule out severe ALG1 deficiency.PMC110787131U54NS115198‐01U54 NS115198Sadek MMorava EBosnyak IRanatunga WKozicz TfalseNormal transferrin glycosylation does not rule out severe ALG1 deficiency.ALG1-CDG is a rare, clinically variable metabolic disease, caused by the defect of adding the first mannose (Man) to N-acetylglucosamine (GlcNAc₂)-pyrophosphate (PP)-dolichol to the growing oligosaccharide chain, resulting in impaired N-glycosylation of proteins. N-glycosylation has a key role in functionality, stability, and half-life of most proteins. Therefore, congenital defects of glycosylation typically are multisystem disorders. Here we report a 3-year-old patient with severe neurological, cardiovascular, respiratory, musculoskeletal and gastrointestinal symptoms. ALG1-CDG was suggested based on exome sequencing and Western blot analysis. Despite her severe clinical manifestations and genetic diagnosis, serum transferrin glycoform analysis was normal. Western blot analysi2024-01-01T00:00:00Z2024 May2026-06-03T06:49:15.334Z2026-04-25T03:21:52.007ZS-EPMC110787133873663310.1002/jmd2.12415