Prence E M, Natowicz M R, Zalewski I
Division of Medical Genetics, E.K. Shriver Center, Waltham, MA 02254.
Clin Chem. 1993 Sep;39(9):1811-4.
Tay-Sachs disease (TSD), an autosomal recessive neurodegenerative condition, is the result of a deficiency of beta-hexosaminidase A (hex A). Heterozygotic individuals are screened by analysis for hex A and hex B activities; the percent of hex A is the critical determinant of carrier vs noncarrier status. Most laboratories use a heat-inactivation assay that exploits the differential thermolability of the isoenzymes. However, we have found a reciprocal relation between the apparent leukocyte hex A activity and the amount of the sample used in the assay; i.e., a significant increase in the percent of hex A activity with decreasing amounts of sample. Three sets of data indicate that this phenomenon was caused by an effect on the hex B isoenzyme and not on hex A. This variation in hex A activity with sample amount was not observed when a hex A-specific substrate was used. This phenomenon was also not seen in assays of leukocytes from carriers for Sandhoff disease, a condition associated with a reduction in the amount of hex B. Finally, when leukocytes from a TSD homozygote, containing almost no hex A, were analyzed, marked increases in the percent of hex A were observed with decreasing sample concentrations. These data indicate that misdiagnoses could result from variations in sample concentrations used for TSD carrier testing and support the view that the leukocyte concentrations used for these assays should be standardized.
泰-萨克斯病（TSD）是一种常染色体隐性神经退行性疾病，是由于β-己糖胺酶A（己糖A）缺乏所致。通过分析己糖A和己糖B的活性来筛查杂合子个体；己糖A的百分比是携带者与非携带者状态的关键决定因素。大多数实验室使用热灭活试验，该试验利用了同工酶不同的热稳定性。然而，我们发现白细胞中己糖A的表观活性与试验中所用样品的量之间存在反比关系；也就是说，随着样品量的减少，己糖A活性的百分比显著增加。三组数据表明，这种现象是由对己糖B同工酶的影响而非对己糖A的影响引起的。当使用己糖A特异性底物时，未观察到己糖A活性随样品量的这种变化。在对桑德霍夫病携带者的白细胞检测中也未见到这种现象，桑德霍夫病是一种与己糖B量减少相关的疾病。最后，当分析几乎不含己糖A的TSD纯合子的白细胞时，随着样品浓度的降低，观察到己糖A的百分比显著增加。这些数据表明，用于TSD携带者检测的样品浓度变化可能导致误诊，并支持这样一种观点，即用于这些检测的白细胞浓度应该标准化。
