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.

中文翻译：

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急性肝卟啉症（AHP）的发病机制和临床特征。

急性肝卟啉症包括四种疾病：急性间歇性卟啉症[AIP]，遗传性结肠卟啉症[HCP]，杂色卟啉症[VP]和由于严重缺乏ALA脱水酶[ADP]而引起的稀有卟啉症。在美国，AIP是最严重且最常见的症状。AIP，HCP和VP是由于常染色体显性遗传异常所致，其中正常肝血红素生物合成基因的错义，无义或其他突变，以及其他环境，营养，激素和遗传因素，可能导致严重缺陷血红素（通路的最终产物）在肝细胞内的一个很小但至关重要的“调节池”中。这种缺陷会导致血红素合成途径的第一个且通常是速率控制的酶δ-或5-氨基乙酰丙酸[ALA]合酶-1的抑制，从而显着上调该关键酶的表达，并显着肝脏ALA的过量生产。此外，除了ADP以外，还有明显的生产过剩的胆磷脂原[PBG]，它是合成链中ALA下游的中间产物，尤其是在HCP和VP中，也是沿路径更远的卟啉原和卟啉。急性卟啉症的主要临床特征是严重的神经性疼痛发作。腹部首先感觉到疼痛，但也可能出现在背部，胸部和四肢。女性的发作要比男性多[约4：1]，通常伴有恶心，呕吐，便秘，心动过速和动脉高压。低钠血症也可能发生。一些患者还描述了疼痛，焦虑，失眠等慢性症状。