Abstract：
Acute hepatic porphyrias (AHPs) are a family of four rare genetic diseases resulting from a deficiency in one of the enzymes involved in heme biosynthesis. AHP patients can experience potentially life-threatening acute attacks, characterized by severe abdominal pain, along with other signs and symptoms including nausea, mental confusion, hyponatraemia, hypertension, tachycardia and muscle weakness. Some patients also experience chronic manifestations and long-term complications, such as chronic pain syndrome, neuropathy and porphyria-associated kidney disease. Most symptomatic patients have only a few attacks in their lifetime; nevertheless, some experience frequent attacks that result in ongoing symptoms and a significant negative impact on their quality of life (QoL). Initial diagnosis of AHP can be made with a test for urinary porphobilinogen, [Formula: see text]-aminolaevulinic acid and porphyrins using a single random (spot) sample. However, diagnosis is frequently missed or delayed, often for years, because the clinical symptoms of AHP are non-specific and mimic other more common disorders. Delayed diagnosis is of concern as some commonly used medications can trigger or exacerbate acute attacks, and untreated attacks can become severe, potentially leading to permanent neurological damage or fatality. Other attack triggers include hormonal fluctuations in women, stress, alcohol and low-calorie diets, which should be avoided in patients where possible. For the management of attacks, intravenous hemin is approved, whereas new therapeutic approaches are currently being investigated as a baseline therapy for prevention of attacks and improvement of QoL. Among these, a novel siRNA-based agent, givosiran, has shown very promising results in a recently concluded Phase III trial and has been approved for the management of AHPs. Here, we propose a challenging case study-with a very unusual pediatric onset of variegate porphyria-as a starting point to summarize the main clinical aspects (namely, clinical manifestations, diagnostic challenges, and therapeutic management) of AHPs, with a focus on the latest therapeutic innovations.
摘要：
急性肝卟啉病（AHP）是四种罕见的遗传病家族，是由于血红素生物合成中涉及的一种酶缺乏而引起的。AHP患者可能会经历潜在的危及生命的急性发作，以严重腹痛为特征，以及其他症状和体征，包括恶心，精神混乱,低钠血症,高血压,心动过速和肌肉无力.一些患者还会出现慢性表现和长期并发症,比如慢性疼痛综合征，神经病变和卟啉症相关的肾脏疾病。大多数有症状的患者一生中只有几次发作；尽管如此，一些患者经历了频繁的发作,导致持续的症状和对其生活质量(QoL)的显著负面影响.AHP的初步诊断可以通过尿胆色素原的测试来进行，[式:见正文]-氨基乙酰丙酸和卟啉,使用单个随机(斑点)样品。然而,诊断经常漏诊或延误，通常是多年,因为AHP的临床症状是非特异性的，类似于其他更常见的疾病。延迟诊断令人担忧，因为一些常用的药物会引发或加剧急性发作，未经治疗的攻击可能会变得严重，可能导致永久性神经损伤或死亡。其他攻击触发因素包括女性荷尔蒙波动，压力，酒精和低热量饮食，患者应尽可能避免。对于攻击的管理，静脉注射血红素被批准，而目前正在研究新的治疗方法作为预防发作和改善QoL的基线疗法。其中,一种新的基于siRNA的药物，Givosiran,在最近结束的III期试验中显示出非常有希望的结果，并已被批准用于AHP的管理。这里,我们提出了一个具有挑战性的案例研究-以非常不寻常的杂色卟啉病儿科发作-作为总结主要临床方面的起点（即，临床表现，诊断挑战，和治疗管理）的AHP，专注于最新的治疗创新。
