Hechtman P, Gordon B A, Ng Ying Kin N M
Pediatr Res. 1982 Mar;16(3):217-22. doi: 10.1203/00006450-198203000-00011.
A patient is described whose clinical course and pathologic features, including massive brain storage of GM2 ganglioside in grey matter, are identical with those of classical Tay-Sachs disease despite normal levels of beta -N-acetyl hexosaminidase and normal isozyme distribution. The kinetic properties and thermolability of the patient's hexosaminidase are normal. Crude extracts of a postmortem sample of patient's liver can catalyze the hydrolysis of 5.1 pmoles of labeled GM2 ganglioside/16 h/mg of protein (control liver = 69.9 pmoles/16 h/mg). Addition of partially purified human liver hexosaminidase A activator protein stimulated the hydrolysis of substrate by the patients liver extract by 27-fold compared to 3-fold for control livers. Measurement of "activator" in enriched fractions of patient's and control liver showed a reduced (25-30% of control) amount of stimulation of hexosaminidase A catalyzed hydrolysis of GM2 ganglioside as well as of Asialo-GM2 ganglioside. The addition of sphingomyelin to reaction mixtures, which is known to inhibit surfactant stimulation of hexosaminidase A, reduced activation of hexosaminidase A by patient's liver preparation to undetectable levels. Polyacrylamide gel electrophoresis of enriched preparations of control and patient's liver showed a rapidly migrating protein band in control liver corresponding to the activator protein and the absence of this protein band in the patient's liver.
本文描述了一名患者，其临床病程和病理特征，包括灰质中大量储存GM2神经节苷脂，与经典泰-萨克斯病相同，尽管β-N-乙酰己糖胺酶水平正常且同工酶分布正常。患者己糖胺酶的动力学特性和热稳定性正常。患者肝脏死后样本的粗提物每毫克蛋白质每16小时可催化水解5.1皮摩尔标记的GM2神经节苷脂（对照肝脏为69.9皮摩尔/16小时/毫克）。加入部分纯化的人肝脏己糖胺酶A激活蛋白后，患者肝脏提取物对底物的水解作用比对照肝脏增强了27倍，而对照肝脏仅增强了3倍。对患者和对照肝脏富集组分中“激活剂”的测量显示，己糖胺酶A催化GM2神经节苷脂以及去唾液酸GM2神经节苷脂水解的刺激量减少（为对照的25%-30%）。已知鞘磷脂可抑制表面活性剂对己糖胺酶A的刺激，向反应混合物中加入鞘磷脂后，患者肝脏制剂对己糖胺酶A的激活作用降至无法检测的水平。对照和患者肝脏富集制剂的聚丙烯酰胺凝胶电泳显示，对照肝脏中有一条快速迁移的蛋白带对应于激活蛋白，而患者肝脏中没有这条蛋白带。
