Klinické projevy a výsledky metabolických a molekulárních analýzu osmi dětí s dědičnou poruchou glykosylace proteinů

Clinical and Molecular Analyses in Eight Children with Congenital Disorders of Glycosylation

In our study we describe the clinical symptoms and the results of biochemical and molecular analyses in eightpatients with CDG syndrome type I.Methods: The nonglycosylated and hypoglycosylated transferrins were measured in serum using turbidimetricimmunoassay and isoelectric focusing. The genes for phosphomannomutase 2 (PMM2) and
-1,3-glukosyltransferase(ALG6) were sequenced.Results: In all patients, increasedamounts of hypo- and nonglycosylated transferrins were observed. The diseaseis manifested in infancy with failure to thrive, muscle hypotonia, epilepsy, microcephaly and psychomotorretardation. In most patients, strabismus and inverted nipples were present and hypoplasia of the cerebellum wasfound in six patients. One boy had cyclic pericardial effusion and another boy was operated on ventricular septaldefect. In most patients, low concentration of antitrombin III, factor XI and protein C and S were found. Theactivities of -glucuronidase, -mannosidase, -hexosaminidase and arylsulfatase A in serum were increased andthe activities of
-mannosidase and -mannosidase in leucocytes were decreased in comparison with controls.Molecular analyses revealed that two siblings were compound heterozygotes for mutations G422A and C357C ingene for phosphomannomutase 2 (PMM2) and also homozygotes for polymorphism IVS5+19 C  T andheterozygotes for polymorphism IVS+22 T  A. One girl is a compound heterozygote for missence mutationsG422A and C338T in the gene forPMM2. Three other patients are heterozygotes for mutations G422A, the secondmutation was not found. In one child, a heterozygous missense mutation T911C was found in the gene for ALG6.Conclusion: The prognosis of children withCDGsyndrome type I is unfavourable.Enzymatic and/ormolecularanalyses are necessary for genetic counseling and for the prenatal diagnosis in affected families.

Key words:
CDG syndrome type Ia, psychotomotor retardation, cerebellar hypoplasia