A new syndrome associated with beta-glucocerebrosidase feficiency : morphological, biochemical, and mollecular genetic studies

最近，我们报道了一种特殊的遗传性储存障碍，题为“一种与β -葡萄糖脑苷酶缺乏和储存细胞马赛克群相关的新综合征”（Acta Neurol Scand 1992; 86: 407-420）。1994年，在McKusick的《孟德尔人遗传》第11版中，该疾病被归类为“MIM 231005：戈歇样病（伪戈歇病）”。1993年，我们利用PCR技术进行了基因研究，发现了β -葡萄糖脑苷酶基因的一个点突变。然而，我们未能检测到诸如Leu-444向Pro、Asp-370向Ser、Pro-415向arg、Val-394向Leu、Ser-364向Thr、Cys-342向Gly和Try-312向Cys等点突变。1994年，我们进行了详细的酶分析，排除了多种酶缺乏症，结果11种酶的活性除β -葡萄糖脑苷酶外均正常。然而，我们发现先证者的脾脏和肝脏中除了葡萄糖神经酰胺外，还有轻微异常的乳糖神经酰胺储存。1995年，我们纯化了鞘脂激活蛋白2 （sphingolipactivator protein 2, SAP-2）并与2型戈谢病患者进行了比较。而先证者与后证者的SAP-2的功能和数量没有差异。我们认为这种新综合征可能是一种毗邻基因综合征，如一种新的小鼠模型，由于突变的meraxin基因与葡萄糖脑苷酶和血栓反应蛋白3相邻。

Recently we reported peculiar unique hereidtary storage disorder entitled "A new syndrome associated with beta-glucocerebrosidase deficiency and a mosaic population of storage cells"(Acta Neurol Scand 1992 ; 86 : 407-420). In 1994, this disorder was classified as "MIM 231005 : Gaucher-like disease (Pseudo-Gaucher disease)" in 1lth edition of McKusick's "Mendelian Inheritance in Man" . In 1993, we performed genetic study using PCR to find a point mutation of the gene foe beta-glucocerebrosidase. However, we failed to detect point mutations such as Leu-444 to Pro, Asp-370 to Ser, Pro-415 to arg, Val-394 to Leu, Ser-364 to Thr, Cys-342 to Gly and Try-312 to Cys. In 1994, we performed enzyme analyzes in detail to exclude multiple enzyme deficiency, while the activity of 11 kind of enzymes were all normal except beta-glucocerebrosidase. However, we determined slight abnormak storage of lactosylceramide in addition to glucosylceramide in the spleen and liver of the proband. In 1995, we purified sphingolipid activator protein 2 (SAP-2) and compared with that of patients with type 2 Gaucher disease.However, there were no difference between the function and amount of SAP-2 in the proband and those of the latter. We suggest that this new syndrome may be a contiguous gene syndrome such as a new murine model due tomutant meraxin gene which contiguous to both glucocerebrosidase and thrombospondin 3.