CDGsairauksiin

Congenital disorders of glycosylation (CDG) are a group of inherited metabolic disorders caused by defects in the glycosylation pathways that attach sugar molecules to proteins and lipids. Because glycosylation is essential for the stability and function of many biological molecules, CDG can affect multiple organ systems. Clinical features are highly variable and can include developmental delay or intellectual disability, hypotonia, failure to thrive, liver dysfunction, coagulation abnormalities, seizures, vision or hearing problems, and endocrine issues. The presentation often changes with age, and some individuals experience fluctuating symptoms.

CDG are traditionally classified into two broad groups, type I and type II, based on where the glycosylation defect occurs. Type I defects disrupt the assembly or transfer of the lipid-linked oligosaccharide precursor in the endoplasmic reticulum, while Type II defects affect processing of the glycan in the Golgi apparatus. Numerous genes have been implicated, with dozens of described subtypes such as PMM2-CDG (historically CDG-Ia), MPI-CDG (CDG-Ib), DPAGT1-CDG, and ALG6-CDG, among others. Some subtypes involve defects in Golgi trafficking or the function of protein complexes required for proper glycosylation.

Diagnosis typically begins with screening tests such as serum transferrin isoelectric focusing or other glycosylation pattern analyses, followed by confirmatory genetic testing (often exome sequencing or targeted gene panels). Prenatal testing may be possible in families with known pathogenic variants.

Management is multidisciplinary and supportive, focusing on associated complications like nutrition, growth monitoring, liver and coagulation issues, and seizure control. A subset of CDG types has targeted therapies; for example, oral mannose can improve symptoms in MPI-CDG (CDG-Ib). Overall prognosis varies widely by subtype and severity, with ongoing research aimed at better diagnostics and therapies.