Prenatal Diagnosis of Lysosomal Storage Disorders by Enzymes Study Using Chorionic Villus and Amniotic Fluid

Abstract

The reported prevalence of lysosomal storage disorder (LSD) is 1:5,000–7,000 live births and with the limited availability of therapeutic option; prenatal diagnosis (PD) remains the only preventable cure for storage disorders. One hundred forty pregnancies having confirmed diagnosis of LSDs in index case were selected for enzymes study during PD from uncultured and/or cultured chorionic villus (CV/CCV) and cultured amniotic fluid (CAF) cells. In seven pregnancies, molecular analysis was additionally carried out where mutation was known in an index case. Of 140 pregnancies, 60 (42.9 %) were diagnosed as affected, 13 (9.3 %) had an intermediate enzyme activity and 67 (47.8 %) had normal enzyme activity. Results were confirmed in 83 cases whereas 57 cases were lost from the follow-up. In one case, enzyme β-galactose-6 sulphate sulphatase specific for Morquio-A disorder [mucopolysaccharidosis-IVA (MPS-IVA)] had shown 30 % reduced activity in CV cells and the case was diagnosed as carrier for MPS-IVA while it delivered an affected child. Further molecular analysis in seven cases that included six with Tay-Sachs and one with Gaucher disease, confirmed the results obtained by enzymatic study during PD. PD of LSDs can be carried out by enzymes study from CV/CCV and CAF with an accuracy of molecular method. However, in cases of MPS and mucolipidosis, Amniotic fluid (AF) is preferred over CV/CCV. In addition, special care is needed while interpreting enzyme results encompassing carrier status and they need to be further evaluated by molecular studies.