Gorodischer R, Davidson R G, Mosovich L L, Yaffe S J
Pediatr Res. 1976 Jul;10(7):650-6. doi: 10.1203/00006450-197607000-00004.
This report deals with quantitative and qualitative investigations of alkaline phosphatase in two unrelated infants with the severe infantile form of hypophosphatasia. Both affected infants had no detectable leukocyte alkaline phosphatase activities and both sets of parents and one sibling tended to have low but variable leukocyte enzyme activities. Normal duodenal juice alkaline phosphatase activity was present in the one patient in whom it was measured and a wide range of variation in enzymic activity was observed in the stools. There was no significant difference in the stool enzyme activity between both patients with hypophosphatasia (42.01 +/- 9.77 U) and control infants (40.55 +/- 6.29 U). However, the heterozygous parents had values significantly lower than the control adults (2.10 +/- 0.47 as compared with 19.10 +/- 4.44 U). Intestinal bacteria did not contribute significantly to the stool alkaline phosphatase activity. Enzyme activity was present in the bile of one of the patients and nearly absent in that of the other. Three "inducers" of alkaline phosphatase were given to both patients (phenobarbital, vitamin A, and corticosteroid). No clinical improvement or rise in serum alkaline phosphatase activity was observed during the trial of therapy with these agents. However, a significant increase in the activity of serum acid phosphatase was demonstrated during the course of vitamin A administration, suggesting an in vivo action of vitamin A on the lysosomes through decreasing the stability of the membrane and releasing acid phosphatase to the serum. Quantitative determination of tissue alkaline phosphatases from autopsy tissues was highly variable: no activity was found in bone, lungs, or spleen of either infant; there was a discrepancy in liver and kidney alkaline phosphatase values (zero in one patient and present in the other) and activity was present in the intestinal mucosa of both. Qualitative analysis of kidney, liver, and intestinal alkaline phosphatase revealed some differences between the patients and control subjects in heat inactivation and phenylalanine inhibition (Table 3). Starch gel electrophoresis of the liver preparation of one patient disclosed a single band which had greater mobility than that of six control subjects matched for age. Liver extracts from a premature and from full term newborns showed two bands. The single band of the patient's liver enzyme corresponded to the newborn's fast moving component. In addition, the intestinal enzyme prepared from the same patient had an extra band when compared with age-matched control subjects.
本报告涉及对两名患有严重婴儿型低磷酸酯酶症的无关婴儿的碱性磷酸酶进行的定量和定性研究。两名患病婴儿均未检测到白细胞碱性磷酸酶活性，两组父母及一名同胞的白细胞酶活性均偏低且存在差异。在其中一名接受检测的患者中，十二指肠液碱性磷酸酶活性正常，且粪便中酶活性存在广泛差异。两名低磷酸酯酶症患者（42.01±9.77 U）与对照婴儿（40.55±6.29 U）的粪便酶活性无显著差异。然而，杂合子父母的值显著低于对照成年人（分别为2.10±0.47 U和19.10±4.44 U）。肠道细菌对粪便碱性磷酸酶活性的贡献不显著。其中一名患者的胆汁中存在酶活性，另一名患者的胆汁中几乎没有。给两名患者使用了三种碱性磷酸酶“诱导剂”（苯巴比妥、维生素A和皮质类固醇）。在使用这些药物进行治疗试验期间，未观察到临床改善或血清碱性磷酸酶活性升高。然而，在给予维生素A的过程中，血清酸性磷酸酶活性显著增加，这表明维生素A在体内通过降低膜稳定性并将酸性磷酸酶释放到血清中对溶酶体产生作用。对尸检组织中的组织碱性磷酸酶进行定量测定结果差异很大：两名婴儿的骨骼、肺部或脾脏均未发现活性；肝脏和肾脏碱性磷酸酶值存在差异（一名患者为零，另一名患者存在活性），且两名患者的肠黏膜均有活性。对肾脏、肝脏和肠道碱性磷酸酶的定性分析显示，患者与对照受试者在热失活和苯丙氨酸抑制方面存在一些差异（表3）。对一名患者肝脏制剂进行淀粉凝胶电泳显示有一条带，其迁移率高于六名年龄匹配的对照受试者。早产和足月新生儿的肝脏提取物显示有两条带。该患者肝脏酶的单条带对应于新生儿的快速移动成分。此外，与年龄匹配的对照受试者相比，同一患者制备的肠道酶有一条额外的带。
