Dědičné poruchy glykosylace proteinů typ Ia:klinická, biochemická a molekulární charakteristikau dvou sourozenců s hypoplazií mozečku

Congenital Disorders of Glycosylation Type Ia: Clinical, Biochemicaland Molecular Analyses in Two Siblings with Cerebellar Hypoplasia

Backround.
Congenital disorders of glycosylation (CDG syndrome) represent a newly delineated group of inheriteddiseases of glycoprotein synthesis. We present results of biochemical and molecular analyses in two Czech patientswith CDG Ia syndrome.Methods andResults. Serumconcentrations of the nonglycosylated and hypoglycosylated transferrinweremeasuredusing turbidimetric immunoassay. In positive patients, the isoelectric focusing of serum transferrin and molecularanalyses of the gene for phosphomannomutase 2 were performed. The disease manifested in both children in infancywith failure to thrive, inverted nipples, strabismus, epilepsy, muscle hypotonia, microcephaly, psychomotor retardationand hypoplasia of the cerebellum. The biochemical investigation revealed elevated liver enzymes, lowconcentration of factor XI and protein S. In one child lower concentration of the antithrombin III and protein C werefound. Activities of arylsulfatase A and β-glucuronidase in serum were higher and activity of α-mannosidase inleucocytes was lower in comparison with controls. Molecular analyses revealed that both children are compoundheterozygotes for the mutation 422G>A and 357C>A in gene for phosphomanomutase 2. Both siblings are alsohomozygotes 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 arenecessary for genetic counselling and the prenatal diagnosis.

Key words:
CDG Ia, psychomotor retardation, failure to thrive, cerebellar hypoplasia.