Becker D M, Kramer S
Medicine (Baltimore). 1977 Sep;56(5):411-23. doi: 10.1097/00005792-197709000-00003.
The hereditary hepatic porphyrias, PV, AIP and HC, are characterized biochemically by increased excretion of porphyrins and the porphyrin precursors ALA and PBG. They are characterized clinically by episodes of acute neurological involvement. The increased production of porphyrins and porphyrin precursors has been shown to be due to partial enzyme blocks along the heme biosynthetic pathway which results in secondary depression of the key enzyme ALA-synthetase. The neurological manifestations could therefore be related to either a decrease in essential heme-proteins or other heme-containing compounds within the nervous system, or to a toxic effect of the over-production of the porphyrin precursors ALA and PBG. There is evidence for and against both theories. Recent work from a number of research groups has shown the porphyrin precursors to have potent pharmacological effects on the nervous system, and these are possibly related to the GABA receptor and binding site-porphyrin precursor interactions. Current studies on therapy of the acute attack have concentrated on suppression of ALA-synthetase activity, and consequently, on reduced ALA and PBG production. A number of such methods of therapy have met with remarkable success and hold promise for the future treatment of the acute attack.
遗传性肝卟啉病，即迟发性皮肤卟啉病（PV）、急性间歇性卟啉病（AIP）和遗传性粪卟啉病（HC），其生化特征为卟啉以及卟啉前体δ-氨基-γ-酮戊酸（ALA）和卟胆原（PBG）的排泄增加。它们的临床特征为急性神经受累发作。已表明卟啉和卟啉前体产量增加是由于血红素生物合成途径中的部分酶阻断，这导致关键酶ALA合酶继发性抑制。因此，神经学表现可能与神经系统内必需血红素蛋白或其他含血红素化合物的减少有关，或者与卟啉前体ALA和PBG过量产生的毒性作用有关。两种理论都有支持和反对的证据。多个研究小组最近的研究表明，卟啉前体对神经系统具有强大的药理作用，这些作用可能与γ-氨基丁酸（GABA）受体以及结合位点 - 卟啉前体相互作用有关。目前对急性发作治疗的研究集中在抑制ALA合酶活性，从而减少ALA和PBG的产生。许多这样的治疗方法已经取得了显著成功，并为急性发作的未来治疗带来了希望。
