Studies of porphyrin metabolic disorder and early diagnosis in porphyria with photodermatological manifestation.

1.卟啉病早期诊断方法的研究进展。我建立了一种高效液相色谱法测定尿液、外周血和粪便中卟啉的方法。该方法可作为卟啉症患者筛查诊断的常规方法.本文对60例卟啉病患者进行了临床和生物学研究，测定了8种血红素生物合成酶中5种酶的活性，以及肝活检物中卟啉类化合物及其前体物ALA和PBG的含量，并对卟啉代谢异常的机理进行了探讨。检测骨髓和外周血。在本研究中，我们设计或发展了一些新的方法和实验技术，发现PCT患者的肝ALA脱氢酶活性明显降低。总结目前关于ALA脱氢酶的实验，认为酶活性的降低是由于酶蛋白质的减少引起的。从目前的大鼠实验中发现，与对照组相比，酒精、雌激素和六氯苯处理的大鼠的肝脏ALA脱氢酶活性没有变化，作者认为PCT患者与实验性PCT患者存在酶活性差异，发现2例PCT患者红细胞URO'gen脱羧酶活性明显降低，并对15例患者进行了血红素生物合成酶活性及卟啉代谢产物的测定EPP中VP 6例，CP 7例。结果表明，在VP中ALA合成酶活性显著增加。为卟啉病的诊断提供了基础资料.卟啉症的临床统计。本文收集了日本所有已报道的卟啉病病例，并对其进行了临床统计和流行病学观察，以总结日本卟啉病的现状。

1. The development of method in early stage of porphyria. I established a method of simultaneaus measurement of urinary, pheripheral blood, and fecal porphyrins by high-performance liquid chromatography. This method can be used as a routine method for mass screening of diagnosis in patients with porphyria.2. The mechanism of abnormalities of porphyrin metabolism in four types of porphyria with photodermatological manifestation.Approximately 60 cases in porphyrias obtained were subjected to the clinical and biological investigations, in which the activities of five enzymes out from the eight heme biosynthetic enzymes and also the content of porphyrins and two precursors, ALA and PBG in the bioptic materials from liver, bone marrow and peripheral blood were determined. Several methods and experimental techniques were newly devised or developed during this study.Hepatic ALA dehydratase activity in PCT patients were markedly decreased. Summarizing the present experiments on ALA dehydratase enzyme, the decrease activity to be caused by a decreased in the enzyme protein. From the present rat experiments, it was found that alcohol, estrogen and hexachlorobenzene treated rats showed no change in hepatic ALA dehydratase activity compared to controls, postulating an enzymatic discrepancy between PCT patients and experimental PCT.Two cases that markedly decreased of erythrocyte URO'gen decarboxylase activity was found in PCT patients.The enzymes activities and porphyrin metabolites of heme biosynthesis were determined in 15 patients in EPP, 6 cases of VP and 7 cases of CP. As the results, ALA synthase activity was found to be markedly increased in VP. Furthermore, author made a basic data for diagnosis of porphyrias.3. The clinical statistics in porphyrias. All the cases of porphyria ever reported in Japan were collected and subjected to clinical statistics and epidemiological observation in order to summarize the current informations about porphyrias in Japan.