PRENATÁLNÍ DIAGNOSTIKA LYSOZOMÁLNÍCHENZYMOPATIÍ V ČESKÉ REPUBLICE

Prenatal Diagnosis of Lysosomal Enzymopathies in the CzechRepublic

Background.
Prenatal diagnosisi represents the important fprm of prevention of the inherited metabolic diseasesand its accessibility becomes the most effective assistance to involved families. The aim of the study was to introduceprenatal diagnisis of major inherited lysosomal disorders of the group of lipidoses, micopolysaccharidoses, glycop-roteinoses, and mucolipidoses.Methods and Results. Methodological approach is based on the activity estimation of the specific lysosomalhydrolases that are missing or inactive. Methods were extended by a set of supportive analyses, namely byultrastructural identification of the lysosomal storage of the non-degraded substrate, DNA analysis showing mutationin the family or by biochemical analysis of the amniotic fluid. Uncultured cultured chorionic villi, cultured amnioticfluid cells yand samples of the amniotic fluid were examined. Altogether 17 pregnancies at risk for seven differentlysosomal enzymopathies were followed: GM2 gangliosidosis (2 cases), Fabra disease (3 cases), Krabbe disease (1case), Niemann-Pick disease type A (1 case), mucopolysaccharidosis I (5 cases), mucopolysaccharidosis II (4 cases),mucolipidosis II (I-cell disease) (1 case). Profound deficiency of enzyme activities (a-galactosidase A in fabrydisease, galactocerebrosidase in Krabbe disease, a-iduronidase in mucopolysaccharidosis I) was identified in threepregnancies, which were terminated on the mother´s decision. The diagnose was confirmed by the biochemicalanalysis of tissues of aborted foetuses. In two of them (Fabry disease, mucopolysaccharidosis I) ultrastructural singsof storage werw proved. In two cases the foetal heterozygote state was identified. In case at risk for Niemann-Pickdisease type A, the diagnosis was confirmed also by DNA analysis. In the pregnancy at risk for Fabry disease,heterozygous state was confirmed indirectly according to the difference of a-galactosidase activities in cultured anduncultured cells. A set control values of enzyme activities in individual types of processed material (native andcultured chorionic villi, cultured amniocytes, and amniotic fluid supernatant) has been established.Conclusions. Inherited lysosomal enzymopathies represent important indication for prenatal diagnosis availablenow in our department. Condicio sine qua non is the biochemical or molecular genetic confirmation of diagnosis inthe family involved.

Key words:
prenatal diagnosis, inherited lysosomal enzymopathies, chorionoc villi, amniocytes, enzyme analysis,