title: Rapid detection of fetal Mendelian disorders: Tay-Sachs disease.
abstract: Tay-Sachs disease is an autosomal recessive storage disease caused by the impaired activity of the lysosomal enzyme hexosaminidase A. In this fatal disease, the sphingolipid GM2 ganglioside accumulates in the neurons. Due to high carrier rates and the severity of the disease, population screening and prenatal diagnosis of Tay-Sachs disease are routinely carried out in Israel. Laboratory diagnosis of Tay-Sachs is carried out with biochemical and DNA-based methods in peripheral and umbilical cord blood, amniotic fluid, and chorionic villi samples. The assay of hexosaminidase A (Hex A) activity is carried out with synthetic substrates, 4-methylumbelliferyl-6-sulfo-N-acetyl-beta-glucosaminide (4-MUGS) and 4-methylumbelliferil-N-acetyl-beta-glucosamine (4-MUG), and the DNA-based analysis involves testing for the presence of specific known mutations in the alpha-subunit gene of Hex A. Prenatal diagnosis of Tay-Sachs disease is accomplished within 24-48 h from sampling. The preferred strategy is to simultaneously carry out enzymatic analysis in the amniotic fluid supernatant or in chorionic villi and molecular DNA-based testing in an amniotic fluid cell-pellet or in chorionic villi.
authors.affiliation: Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Esther
authors.initials: E
authors.lastname: Guetta
authors.forename: Leah
authors.initials: L
authors.lastname: Peleg
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000378:metabolism; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000201:enzymology; D001681:Biological Assay; D002824:Chorionic Villi / Q000201:enzymology; D015193:Chorionic Villi Sampling; D004252:DNA Mutational Analysis; D005260:Female; D005312:Fetal Blood / Q000201:enzymology; D018507:Gene Expression Regulation, Developmental; D005820:Genetic Testing; D006801:Humans; D006923:Hymecromone / Q000031:analogs & derivatives / Q000378:metabolism; D009154:Mutation; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D015203:Reproducibility of Results; D013379:Substrate Specificity; D013661:Tay-Sachs Disease / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D013997:Time Factors; D054820:beta-Hexosaminidase alpha Chain / Q000235:genetics / Q000378:metabolism
chemical_list: C025158:4-methylumbelliferyl 2-acetamido-2-deoxy-beta-D-glucopyranoside; D006923:Hymecromone; C043647:4-methylumbelliferyl-6-sulfo-2-acetamido-2-deoxy-beta-glucopyranoside; C518253:HEXA protein, human; D054820:beta-Hexosaminidase alpha Chain; D000117:Acetylglucosamine