The acute hepatic porphyrias (AHPs) include three autosomal dominant disorders, acute intermittent porphyria, variegate porphyria and hereditary coproporphyria, and the ultra‐rare autosomal recessive 5‐aminolevulinic acid dehydratase‐deficient porphyria. All four are characterized by episodic acute neurovisceral attacks that can be life‐threatening if left untreated. The attacks are precipitated by factors that induce hepatic 5‐aminolevulinic acid synthase 1 (ALAS1), resulting in accumulation of the porphyrin precursors, 5‐aminolevulinic acid and porphobilinogen, which are believed to cause neurotoxicity. Diagnosis of these rare disorders is often delayed because the symptoms are non‐specific with many common aetiologies. However, once clinical suspicion of an AHP is raised, diagnosis can be made by specialized biochemical testing, particularly during attacks. Moderate or severe attacks are treated with intravenous hemin infusions, together with supportive care to relieve pain and other symptoms. Prophylactic treatments are recommended in patients with confirmed recurrent attacks (≥4 attacks in a maximum period of 12 months), the most effective being givosiran, an RNAi therapeutic targeting hepatocyte ALAS1 mRNA. AHP patients with clinically and/or biochemically active disease are at elevated risk for developing long‐term complications, including chronic kidney disease, chronic hypertension and hepatocellular carcinoma, thus, surveillance is recommended. Here, using a case‐based format, we provide an update on the pathogenesis, diagnosis and treatment of the AHPs based on literature review and clinical experiences.

中文翻译：

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急性肝卟啉症的病例讨论：发病机制、诊断和治疗的最新进展

急性肝卟啉症（AHP）包括三种常染色体显性遗传性疾病：急性间歇性卟啉症、杂色卟啉症和遗传性粪卟啉症，以及极其罕见的常染色体隐性遗传 5-氨基乙酰丙酸脱水酶缺陷型卟啉症。这四种疾病的特点都是突发性急性神经内脏发作，如果不及时治疗可能会危及生命。这些攻击是由诱导肝 5-氨基乙酰丙酸合酶 1 (ALAS1) 的因素引发的，导致卟啉前体、5-氨基乙酰丙酸和胆色素原的积累，这被认为会引起神经毒性。这些罕见疾病的诊断常常被延迟，因为许多常见病因的症状不具有特异性。然而，一旦临床上怀疑 AHP，可以通过专门的生化测试做出诊断，特别是在发作期间。中度或重度发作可通过静脉输注血红素以及支持性护理来治疗，以缓解疼痛和其他症状。建议对确诊的复发性发作（最长 12 个月内发作≥4 次）的患者进行预防性治疗，最有效的是 givosiran，一种针对肝细胞的 RNAi 治疗药物阿拉斯1mRNA。患有临床和/或生化活动性疾病的 AHP 患者发生长期并发症的风险较高，包括慢性肾病、慢性高血压和肝细胞癌，因此建议进行监测。在这里，我们采用基于病例的形式，根据文献回顾和临床经验，提供 AHP 发病机制、诊断和治疗的最新信息。