Section on Gastroenterology & Hepatology, and Molecular Medicine & Translational Science, Wake Forest University School of Medicine/NC Baptist Hospital, Winston-Salem, NC 27157, United States of America.
Section on Hematology & Oncology, Wake Forest University School of Medicine/NC Baptist Hospital, Winston-Salem, NC 27157, United States of America.
Mol Genet Metab. 2019 Nov;128(3):213-218. doi: 10.1016/j.ymgme.2019.03.002. Epub 2019 Mar 6.
The acute hepatic porphyrias include four disorders: acute intermittent porphyria [AIP], hereditary coproporphyria [HCP], variegate porphyria [VP], and the rare porphyria due to severe deficiency of ALA dehydratase [ADP]. In the USA, AIP is the most severe and most often symptomatic. AIP, HCP, and VP are due to autosomal dominant genetic abnormalities, in which missense, nonsense, or other mutations of genes of normal hepatic heme biosynthesis, in concert with other environmental, nutritional, hormonal and genetic factors, may lead to a critical deficiency of heme, the end-product of the pathway, in a small but critical 'regulatory pool' within hepatocytes. This deficiency leads to de-repression of the first and normally rate-controlling enzyme of the heme synthetic pathway, delta- or 5-aminolevulinic acid [ALA] synthase-1, and thus to marked up-regulation of this key enzyme and to marked hepatic overproduction of ALA. In addition, except for ADP, there is marked overproduction as well of porphobilinogen [PBG], the intermediate immediately downstream of ALA in the synthetic chain, and, especially in HCP and VP, also porphyrinogens and porphyrins farther down the pathway. The major clinical features of the acute porphyrias are attacks of severe neuropathic-type pain. Pain is felt first and foremost in the abdomen but may also occur in the back, chest, and extremities. Attacks are more common in women than in men [ratio of about 4:1], often accompanied by nausea, vomiting, constipation, tachycardia, and arterial hypertension. Hyponatremia may also occur. Some patients also describe chronic symptoms of pain, anxiety, insomnia, and others.
急性间歇性卟啉症（AIP）、遗传性粪卟啉症（HCP）、变异性卟啉症（VP）和罕见的由于严重缺乏 ALA 脱水酶（ADP）引起的卟啉症。在美国，AIP 是最严重和最常出现症状的。AIP、HCP 和 VP 是由于常染色体显性遗传异常引起的，其中错义、无义或其他突变正常肝血红素生物合成基因，与其他环境、营养、激素和遗传因素一起，可能导致在肝细胞内一个小但关键的“调节池”中血红素（该途径的终产物）严重缺乏。这种缺乏导致血红素合成途径的第一个和正常限速酶δ-或 5-氨基酮戊酸[ALA]合酶-1 的去阻遏，从而导致该关键酶的显著上调和 ALA 在肝脏中的大量产生。此外，除了 ADP 之外，还有明显的卟胆原[PBG]产生过多，PBG 是合成链中 ALA 的下游中间产物，特别是在 HCP 和 VP 中，还有卟啉原和更远的途径中的卟啉。急性卟啉症的主要临床特征是严重的神经型疼痛发作。疼痛首先和最主要地发生在腹部，但也可能发生在背部、胸部和四肢。发作在女性中比在男性中更常见[比例约为 4:1]，常伴有恶心、呕吐、便秘、心动过速和动脉高血压。低钠血症也可能发生。一些患者还描述了慢性疼痛、焦虑、失眠等症状。
