Dědičné poruchy glykosylace

Congenital Disorders of Glycosylation (CDG)

The number of known types of hereditary metabolic disorders is increasing every year and also new groups of these genetic disorders are revealed. The latter include also the recently described disorders of protein glycosylation (congenital disorders of glycosylation, CDG) which comprise n extensive heterogenous group of diseases. The associated clinical symptoms can be typical (e.g. abnormal fat pads on the buttocks); however they are usually, very varied and non-specific; they influence the development of different tissues and organs, in particular functions of the central and peripheral nervous system, frequently with a fatal outcome. Biochemical analysis is therefore the basis of diagnosis: hypoglycosylation (with reduction or absence of the carbohydrate side-chain) is usually assessed by examination of serum transferrin where typical changes of the ratio of its iso-forms make it possible to differentiate the majority of patients from healthy subjects. Since 1995 when the first deficient enzyme of this group was identified, in various countries, selective screening of CDG is gradually introduced, usually by the method of isoelectric focusing. For differentiation of particular types (CDG Ia-Ie, IIa-IIc)? other methods must be used. The assumed frequency of this disease is rather high (1 : 10 -⁠ 40 thousand newborn infants). Due to the unspecific symptoms the defect is however usually not diagnosed. Screening of CDG should be therefore done in all subjects with obscure clinical symptoms in any age group. So far only type Ib can be successfully treated (daily oral mannose administration) and some variants of type II (by administration of fucose). There is the possibility of prenatal diagnosis, in some types heterozygotes can be identified.

Key words:
glycoproteins, defective glycosylation, inborn errors of metabolism