HETEROZYGOTE SCREENING IN TAY-SACHS DISEASE (TSD): A DUALITY CONTROL STUDY

Abstract

Thirteen centers in the U.S. and Canada, involved in TSD heterozygote screening, agreed to participate in a “blind” quality control study. Serum and WBC samples were prepared from 10 obligate TSD carriers (C) and 9 noncarriers (NC). Each lab received 4-6 C and 4-6 NC frozen serum aliquots and a similar number of WBC pellets (all samples: code-labelled). Raw data, methods used, and diagnosis for each sample was reported by each center.Methods for quantification of serum Hex A varied, but did not appear to affect accuracy. Of 64C samples, 60(94%) were diagnosed C; 3(4.7%) were designated inconclusive (I)-all in 1 lab; and 1(1.6%) was identified incorrectly as NC. A false positive frequency of 0.000 (with 75NC sera) and a false negative rate of 0.016 are evident with serum testing.A serious problem (and its subsequent resolution) was uncovered by the WBC data. Although 81 of 81 NC pellets were correctly identified, 13 of 66C samples (19.7%) were called NC. Seven of 13 centers made no errors. The cause of this aberration has been shown to be high g centrifugation of WBC homogenates which preferentially reduces Hex B and results in an apparent increase in Hex A (making C → NC).This study indicates a high, altho not perfect, level of accuracy, with serum screening. With appropriate modification, WBC analysis is also highly accurate. Surveillance of testing programs is critical for (a) monitoring testing accuracy (b) rapidly identifying and helping to correct technical problems, and (c) assuring that quality service is rendered the consumer.