School of Medicine, Cardiff University, Cardiff, UK.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA.
Liver Int. 2024 Sep;44(9):2144-2155. doi: 10.1111/liv.15960. Epub 2024 May 20.
We describe developments in understanding of the porphyrias associated with each step in the haem biosynthesis pathway and the role of individuals whose contributions led to major advances over the past 150 years. The first case of erythropoietic porphyria was reported in 1870, and the first with acute porphyria in 1889. Photosensitisation by porphyrin was confirmed by Meyer-Betz, who self-injected haematoporphyrin. Günther classified porphyrias into haematoporphyria acuta, acuta toxica, congenita and chronica. This was revised by Waldenström into porphyria congenita, acuta and cutanea tarda, with the latter describing those with late-onset skin lesions. Waldenström was the first to recognise porphobilinogen's association with acute porphyria, although its structure was not solved until 1953. Hans Fischer was awarded the Nobel prize in 1930 for solving the structure of porphyrins and the synthesis of haemin. After 1945, research by several groups elucidated the pathway of haem biosynthesis and its negative feedback regulation by haem. By 1961, following the work of Watson, Schmid, Rimington, Goldberg, Dean, Magnus and others, aided by the availability of modern techniques of porphyrin separation, six of the porphyrias were identified and classified as erythropoietic or hepatic. The seventh, 5-aminolaevulinate dehydratase deficiency porphyria, was described by Doss in 1979. The discovery of increased hepatic 5-aminolaevulinate synthase activity in acute porphyria led to development of haematin as a treatment for acute attacks. By 2000, all the haem biosynthesis genes were cloned, sequenced and assigned to chromosomes and disease-specific mutations identified in all inherited porphyrias. These advances have allowed definitive family studies and development of new treatments.
我们描述了对血红素生物合成途径中每一步相关卟啉症的理解的发展，以及在过去 150 年中做出重大贡献的个人的作用。1870 年报道了首例红细胞生成性卟啉症，1889 年报道了首例急性卟啉症。Meyer-Betz 通过自身注射血红素证实了卟啉的光致敏作用。Günther 将卟啉症分为急性血红素卟啉症、急性毒性卟啉症、先天性卟啉症和慢性卟啉症。Waldenström 将其修订为先天性卟啉症、急性卟啉症和迟发性皮肤卟啉症，后者描述了那些发病较晚的皮肤损伤患者。Waldenström 是第一个认识到卟啉原与急性卟啉症有关的人，尽管其结构直到 1953 年才被解决。1930 年，Hans Fischer 因解决卟啉结构和血红素合成问题而获得诺贝尔化学奖。1945 年后，几个研究小组的研究阐明了血红素生物合成途径及其对血红素的负反馈调节。到 1961 年，在 Watson、Schmid、Rimington、Goldberg、Dean、Magnus 等人的工作基础上，加上现代卟啉分离技术的应用，确定了六种卟啉症，并将其分类为红细胞生成性或肝性卟啉症。1979 年，Doss 描述了 5-氨基酮戊酸脱水酶缺乏性卟啉症。急性卟啉症中肝 5-氨基酮戊酸合酶活性增加的发现导致了血红素作为急性发作治疗方法的发展。到 2000 年，所有血红素生物合成基因均被克隆、测序并分配到染色体上，并在所有遗传性卟啉症中确定了疾病特异性突变。这些进展使得能够进行明确的家族研究和开发新的治疗方法。
