title: Population-based Tay-Sachs screening among Ashkenazi Jewish young adults in the 21st century: Hexosaminidase A enzyme assay is essential for accurate testing.
abstract: Tay-Sachs disease (TSD) carrier screening, initiated in the 1970s, has reduced the birth-rate of Ashkenazi Jews with TSD worldwide by 90%. Recently, several nationwide programs have been established that provide carrier screening for the updated panel of Jewish genetic diseases on college campuses and in Jewish community settings. The goals of this study were to determine the performance characteristics of clinical TSD testing in college- and community-based screening programs and to determine if molecular testing alone is adequate in those settings. Clinical data for TSD testing were retrospectively anonymized and subsequently analyzed for 1,036 individuals who participated in these programs. The performance characteristics of the serum and the platelet Hexosaminidase assays were compared, and also correlated with the results of targeted DNA analysis. The serum assay identified 29 carriers and the platelet assay identified 35 carriers for carrier rates of 1/36 and 1/29, respectively. One hundred sixty-nine samples (16.3%) were inconclusive by serum assay in marked contrast to four inconclusive samples (0.4%) by the platelet assay. Molecular analysis alone would have missed four of the 35 carriers detected by the platelet assay, yielding a false negative rate of 11.4% with a sensitivity of 88.6%. Based on the results of this study, platelet assay was superior to serum with a minimal inconclusive rate. Due to changing demographics of the Ashkenazi Jewish population, molecular testing alone in the setting of broad-based population screening programs is not sufficient, and biochemical analysis should be the assay of choice.
authors.affiliation: Genetics Division, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141, USA. schneida@einstein.edu
authors.forename: Adele
authors.initials: A
authors.lastname: Schneider
authors.forename: Sachiko
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Rosanne
authors.initials: R
authors.lastname: Keep
authors.forename: Darnelle
authors.initials: D
authors.lastname: Dorsainville
authors.forename: Joel
authors.initials: J
authors.lastname: Charrow
authors.forename: Kirk
authors.initials: K
authors.lastname: Aleck
authors.forename: Jodi
authors.initials: J
authors.lastname: Hoffman
authors.forename: Sherman
authors.initials: S
authors.lastname: Minkoff
authors.forename: David
authors.initials: D
authors.lastname: Finegold
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Andrew
authors.initials: A
authors.lastname: Spencer
authors.forename: Johannah
authors.initials: J
authors.lastname: Lebow
authors.forename: Jie
authors.initials: J
authors.lastname: Zhan
authors.forename: Stephen
authors.initials: S
authors.lastname: Apfelroth
authors.forename: Nicole
authors.initials: N
authors.lastname: Schreiber-Agus
authors.forename: Susan
authors.initials: S
authors.lastname: Gross
mesh_terms: D001792:Blood Platelets / Q000201:enzymology; D004252:DNA Mutational Analysis; D003710:Demography; D057075:Enzyme Assays / Q000379:methods*; D006579:Heterozygote; D054818:Hexosaminidase A / Q000097:blood / Q000235:genetics*; D049674:History, 21st Century; D006801:Humans; D007585:Jews / Q000235:genetics*; D008403:Mass Screening / Q000379:methods*; D009154:Mutation / Q000235:genetics; D013661:Tay-Sachs Disease / Q000175:diagnosis* / Q000201:enzymology*; D055815:Young Adult
chemical_list: D054818:Hexosaminidase A