Kleijer W J, Geilen G C, Janse H C, van Diggelen O P, Zhou X Y, Galjart N J, Galjaard H, d'Azzo A
Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands.
Pediatr Res. 1996 Jun;39(6):1067-71. doi: 10.1203/00006450-199606000-00022.
Deficiency of lysosomal protective protein/cathepsin A in humans is the primary cause of galactosialidosis, a lysosomal storage disease characterized by combined deficiency of beta-galactosidase and neuraminidase. We have investigated 20 galactosialidosis patients and nine of their obligate heterozygous parents. A group of 12 patients with the early infantile type of the disease exhibited practically complete absence of cathepsin A activity, whereas eight patients with either the late infantile or the juvenile/adult type had 2-5% residual activity. Highest levels (5%) were present in two patients with milder clinical manifestations and later onset of the disease. In most fibroblast strains, beta-galactosidase activity was 10-15% of normal levels, whereas neuraminidase was reduced to less than 4%. Interestingly, a substantial residual activity (10%) of the latter enzyme was detected in the patient with the mildest phenotype and the highest cathepsin A activity. Heterozygous values for cathepsin A were reduced on average to half of normal levels. However, in two cell strains, the activity was far below control range, and in these cases, neuraminidase activity was severely depressed. Finally, we showed that cathepsin A had considerable activity in chorionic villi and amniocytes, but was deficient in amniocytes from a pregnancy with an affected fetus, indicating the relevance of cathepsin A assay for prenatal diagnosis of galactosialidosis.
人类溶酶体保护蛋白/组织蛋白酶A缺乏是半乳糖唾液酸贮积症的主要病因，这是一种溶酶体贮积病，其特征是β-半乳糖苷酶和神经氨酸酶联合缺乏。我们研究了20例半乳糖唾液酸贮积症患者及其9名必然的杂合子父母。一组12例早期婴儿型疾病患者几乎完全缺乏组织蛋白酶A活性，而8例晚期婴儿型或青少年/成人型患者有2 - 5%的残余活性。两名临床表现较轻且发病较晚的患者中组织蛋白酶A活性最高（5%）。在大多数成纤维细胞株中，β-半乳糖苷酶活性为正常水平的10 - 15%，而神经氨酸酶活性降至4%以下。有趣的是，在表型最轻且组织蛋白酶A活性最高的患者中检测到后者酶有相当大的残余活性（10%）。组织蛋白酶A的杂合子值平均降至正常水平的一半。然而，在两个细胞株中，其活性远低于对照范围，在这些情况下，神经氨酸酶活性严重降低。最后，我们表明组织蛋白酶A在绒毛膜绒毛和羊水中有相当活性，但来自患病胎儿妊娠的羊水中该酶缺乏，这表明组织蛋白酶A检测对半乳糖唾液酸贮积症产前诊断的相关性。
