Congenital disorders of glycosylation (CDG syndrome) are hereditary defects of glycoprotein biosynthesis and are genetic metabolic defects. These are usually severe multi-organ diseases with often pronounced neurological disorders. Various subtypes of CDG syndrome are known, which have been grouped according to the location of the respective defect within the cell and not according to clinical aspects. Using NGS panel diagnostics, 43 genes for different CDG types can currently be examined.
The most common is CDG syndrome type Ia, caused by a phosphomannomutase deficiency due to mutations in the PMM2 gene. A prominent developmental disorder is typical; brain malformations, skeletal anomalies, inverted nipples, coagulation defects and other symptoms may also occur. The suspected diagnosis is usually assessed first using metabolic diagnosis to detect abnormal glycosylation of serum glycoproteins by serum transferrin electrophoresis, and then confirmed by molecular genetic examination. However, evidence of abnormal glycosylation of serum glycoproteins is not present in all types of CDG syndrome. Therefore, if the serum transferrin electrophoresis is inconspicuous and the suspicion persists, NGS panel diagnostics may be indicated and may lead to a diagnosis in individual cases and to more precise statements on the prognosis and the risk of recurrence.
Gilfix B.M. 2019, Hum Mutat. 40:1010 / Francisco et al. 2019, J Inherit Metab Dis. 42:29 / Francisco et al. 2019, Mol Genet Metab. 126:1 / van Tol et al. 2019, Curr Opin Struct Biol. 56:107 / Chang et al. 2018, Ann Transl Med. 6:477