[Congenital disorder of type Ia protein glycosylation: clinical, biochemical and molecular characteristics in 2 siblings with cerebellar hypoplasia]. / Dedicné poruchy glykosylace proteinu typ Ia: klinická, biochemická a molekulární charakteristika u dvou sourozencu s hypoplazií mozecku.

BACKGROUND: Congenital disorders of glycosylation (CDG syndrome) represent a newly delineated group of inherited diseases of glycoprotein synthesis. We present results of biochemical and molecular analyses in two Czech patients with CDG Ia syndrome. METHODS AND RESULTS: Serum concentrations of the nonglycosylated and hypoglycosylated transferrin were measured using turbidimetric immunoassay. In positive patients, the isoelectric focusing of serum transferrin and molecular analyses of the gene for phosphomannomutase 2 were performed. The disease manifested in both children in infancy with failure to thrive, inverted nipples, strabismus, epilepsy, muscle hypotonia, microcephaly, psychomotor retardation and hypoplasia of the cerebellum. The biochemical investigation revealed elevated liver enzymes, low concentration of factor XI and protein S. In one child lower concentration of the antithrombin III and protein C were found. Activities of arylsulfatase A and beta-glucuronidase in serum were higher and activity of alpha-mannosidase in leucocytes was lower in comparison with controls. Molecular analyses revealed that both children are compound heterozygotes for the mutation 422G > A and 357C > A in gene for phosphomanomutase 2. Both siblings are also homozygotes for polymorfism IVS5 + 19 C-->T and heterozygygotes for polymorfism IVS5 + 22 T-->A. CONCLUSIONS: The prognosis of children with CDG Ia is unfavourable. Enzymatic and/or molecular studies are necessary for genetic counselling and the prenatal diagnosis.