Glew R H, Gopalan V, Hubbell C A, Beutler E, Geil J D, Lee R E
Department of Biochemistry, School of Medicine, University of New Mexico, Albuquerque 87131.
J Neuropathol Exp Neurol. 1991 Mar;50(2):108-17. doi: 10.1097/00005072-199103000-00002.
Systemic findings such as hepatosplenomegaly and typical Gaucher storage cells in a bone marrow aspirate led to the clinical diagnosis of Gaucher's disease in the seven-year old patient described in this report. On the basis of the lack of neurologic involvement the child was classified as having the Type 1, nonneurologic form of Gaucher's disease. After splenectomy glucocerebrosidase was extracted from her spleen for biochemical analysis. As expected, a marked deficiency of glucocerebrosidase activity was evident in the splenic extract, however her enzyme displayed anomalous behavior compared to other identical splenic preparations from documented Type 1 Gaucher's disease patients in that it failed to reconstitute with the acidic lipid phosphatidylserine. Using the polymerase chain reaction (PCR)-based color complementation assay and restriction endonuclease analysis, we compared the mutation genotype of this child with that of five other classical Type 1 patients. This analysis revealed that our patient alone was homoallelic for a T----C transition at position 1448 in the glucocerebrosidase cDNA that results in a 444Leu----Pro substitution in the glucocerebrosidase protein. The latter mutation genotype is normally associated with the neurologic phenotype, namely, the Types 2 and 3 forms of the disease. The relevance of the nature of polarity in clinical and biochemical analyses is discussed with regard to the phenotypic classification and the future clinical course of disease in the child.
本报告中描述的一名7岁患者出现了全身性表现，如肝脾肿大，骨髓穿刺中发现典型的戈谢贮积细胞，从而临床诊断为戈谢病。基于无神经系统受累，该患儿被归类为患有1型非神经型戈谢病。脾切除术后，从她的脾脏中提取了葡萄糖脑苷脂酶进行生化分析。正如预期的那样，脾脏提取物中明显缺乏葡萄糖脑苷脂酶活性，然而，与来自已确诊的1型戈谢病患者的其他相同脾脏制剂相比，她的酶表现出异常行为，即它不能与酸性脂质磷脂酰丝氨酸重构。使用基于聚合酶链反应（PCR）的颜色互补分析和限制性内切酶分析，我们将该患儿的突变基因型与其他五名经典1型患者的突变基因型进行了比较。分析显示，只有我们的患者在葡萄糖脑苷脂酶cDNA的第1448位存在T----C转换的纯合等位基因，这导致葡萄糖脑苷脂酶蛋白中444Leu----Pro替代。后一种突变基因型通常与神经表型相关，即2型和3型疾病。关于极性性质在临床和生化分析中的相关性，针对该患儿的表型分类和未来疾病临床进程进行了讨论。
