Ben-Yoseph Y, Pack B A, Thomas P M, Nadler H L, Kaback M M
Department of Pediatrics, Wayne State University, Detroit, Michigan 48201.
Am J Med Genet. 1988 Apr;29(4):891-9. doi: 10.1002/ajmg.1320290421.
The diagnostic usefulness of sulfated fluorogenic substrates in carrier detection of Tay-Sachs disease in serum during pregnancy was assessed by testing coded samples. Gradual increase in serum hexosaminidase activities toward these substrates was observed throughout pregnancy in both carrier and non-carriers of the Tay-Sachs gene, but absolute discrimination between the 2 genotypes could not be achieved even when values were compared within the same gestational age. Examination of isolated isozyme fractions with the sulfated substrates showed that the increased activities during pregnancy were due to a genuine increase in hexosaminidase A and not associated with the elevation of hexosaminidase I (or P), which was evident only with unsulfated substrates. The extent of the increase was influenced by the genotype of the fetus as indicated by higher values in pregnant carriers who carried non-carrier fetuses. We conclude that determination of serum hexosaminidase A during pregnancy by sulfated fluorogenic substrates may have a prenatal diagnostic value when used in obligate heterozygotes for Tay-Sachs disease, but is unreliable for screening purposes.
通过对编码样本进行检测，评估了硫酸化荧光底物在孕期血清中泰-萨克斯病携带者检测中的诊断效用。在整个孕期，泰-萨克斯基因携带者和非携带者血清中针对这些底物的己糖胺酶活性均逐渐增加，但即使在相同孕周内比较数值，也无法实现对这两种基因型的绝对区分。用硫酸化底物检测分离的同工酶组分表明，孕期活性增加是由于己糖胺酶A的真正增加，而非与己糖胺酶I（或P）升高相关，后者仅在未硫酸化底物检测时才明显。如携带非携带者胎儿的孕期携带者数值较高所示，增加程度受胎儿基因型影响。我们得出结论，孕期用硫酸化荧光底物测定血清己糖胺酶A，在用于泰-萨克斯病的 obligate 杂合子时可能具有产前诊断价值，但用于筛查目的则不可靠。
