0A-S5-3

 

 

POSTNATAL AND PRENATAL DIAGNOSIS OF LYSOSOMAL STORAGE DISEASES

Shi HP1, Zhang WM1, Guo YF1, Zhao SM2, Sun NH2

1 Institute of Basic Medical Sciences, CAMS, School of Basic Medicine, PUMC, Beijing

2 PUMC Hospital, Beijing

 

Objective: Lysosomal storage diseases (LSD) constitute a group of inherited metabolic diseases, in which lysosomal acid hydrolases are deficient, resulting in accumulation of the substrate of the affected hydrolase within lysosomes. Since there is no definitive treatment for LSD, except Gaucher disease, accurate prenatal diagnosis is the only way to prevent the birth of affected fetuses.

Methods: Microanalysis of enzyme activity is adapted from the Department of clinical genetics, Erasmus University, Rotterdam, the Netherlands. 15 kinds of methods for enzyme assays were set up.

Result: Since 1991,179 index patients were diagnosed based on the characteristic clinical manifestation and specific enzyme assay. Prenatal diagnosis has been carried out in 47 pregnancies at risk of LSD (19 mucopolysaccharidoses, 7 GM1 gangliosidosis, 3 GM2 gangliosidosis,6 metachromatic leukodystrophy, 5 Gaucher disease, 4 Niemann-Pick disease and 3 mucolipidosis) in early pregnancy, 10 affected fetuses were detected Gaucher disease (GD) is the most prevalent LSD. We have performed gene analysis from 10 Chinese patients with GD. Mutation L444P is the most frequent and accounts for 40% of the alleles, which is associated with all type of GD. The genotype of one case is L444P/L444P. His mother had another pregnancy, the prenatal diagnosis was carried out by both enzyme assays and PCR/PFLP. The result is that the fetus is a heterozygote of GD.

Conclusion: Microanalysis of enzyme activity is a reliable method for postnatal and prenatal diagnosis of LSD.