CONGENITAL DISORDERS OF GLYCOSYLATION

Congenital disorders of glycosylation (CDG) are hereditary metabolic disorders caused mainly by disturbances in glycoprotein biosynthesis and often leading to severe neurological symptoms. Numerous subtypes are known and are based on the location of the defect within the cell. The most common form, type Ia, is caused by mutations in the PMM2 gene. Diagnosis is often made by serum transferrin electrophoresis and can be confirmed or expanded by NGS panel diagnostics.

Symptoms

They are usually severe multi-organ diseases with often pronounced neurological disorders.

Subtypes

Various subtypes of CDG syndrome are known, which have been grouped according to the location of the respective defect within the cell rather than according to clinical criteria.

The most common form is CDG type Ia, which is caused by a phosphomannomutase deficiency due to mutations in the PMM2 gene. Typical symptoms include pronounced developmental disorders, which may be accompanied by brain malformations, skeletal abnormalities, inverted nipples, coagulation defects, and other symptoms. The suspected diagnosis is usually made using metabolic diagnosis to detect abnormal glycosylation of serum glycoproteins by serum transferrin electrophoresis, and then confirmed by molecular genetic testing. However, evidence of abnormal glycosylation of serum glycoproteins is not present in all types of CDG. Therefore, if the serum transferrin electrophoresis is inconspicuous and the suspected diagnosis remains, NGS panel diagnostics may be indicated and may lead to a diagnosis in individual cases and thus to more precise statements on the prognosis and the risk of recurrence.

Diagnostics

NGS panel diagnostics can currently examine 43 genes for different CDG types.

References

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