Balwani Manisha, Wang Bruce, Anderson Karl E, Bloomer Joseph R, Bissell D Montgomery, Bonkovsky Herbert L, Phillips John D, Desnick Robert J
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
Department of Medicine, University of California, San Francisco, CA.
Hepatology. 2017 Oct;66(4):1314-1322. doi: 10.1002/hep.29313. Epub 2017 Sep 4.
The acute hepatic porphyrias are a group of four inherited disorders, each resulting from a deficiency in the activity of a specific enzyme in the heme biosynthetic pathway. These disorders present clinically with acute neurovisceral symptoms which may be sporadic or recurrent and, when severe, can be life-threatening. The diagnosis is often missed or delayed as the clinical features resemble other more common medical conditions. There are four major subgroups: symptomatic patients with sporadic attacks (<4 attacks/year) or recurrent acute attacks (≥4 attacks/year), asymptomatic high porphyrin precursor excretors, and asymptomatic latent patients without symptoms or porphyrin precursor elevations. Given their clinical heterogeneity and potential for significant morbidity with suboptimal management, comprehensive clinical guidelines for initial evaluation, follow-up, and long-term management are needed, particularly because no guidelines exist for monitoring disease progression or response to treatment. The Porphyrias Consortium of the National Institutes of Health's Rare Diseases Clinical Research Network, which consists of expert centers in the clinical management of these disorders, has formulated these recommendations. These recommendations are based on the literature, ongoing natural history studies, and extensive clinical experience. Initial assessments should include diagnostic confirmation by biochemical testing, subsequent genetic testing to determine the specific acute hepatic porphyria, and a complete medical history and physical examination. Newly diagnosed patients should be counseled about avoiding known precipitating factors. The frequency of follow-up depends on the clinical subgroup, with close monitoring of patients with recurrent attacks who may require treatment modifications as well as those with clinical complications. Comprehensive care should include subspecialist referrals when needed. Annual assessments include biochemical testing and monitoring for long-term complications. These guidelines provide a framework for monitoring patients with acute hepatic porphyrias to ensure optimal outcomes. (Hepatology 2017;66:1314-1322).
急性肝卟啉病是一组四种遗传性疾病，每种疾病都是由于血红素生物合成途径中特定酶的活性缺乏所致。这些疾病临床上表现为急性神经内脏症状，可能是散发性的或复发性的，严重时可危及生命。由于临床特征与其他更常见的疾病相似，诊断常常被漏诊或延误。有四个主要亚组：散发性发作（每年<4次发作）或复发性急性发作（每年≥4次发作）的有症状患者、无症状的高卟啉前体排泄者以及无症状或卟啉前体无升高的无症状潜伏患者。鉴于其临床异质性以及管理欠佳时出现严重发病的可能性，需要有针对初始评估、随访和长期管理的全面临床指南，特别是因为目前尚无监测疾病进展或治疗反应的指南。美国国立卫生研究院罕见病临床研究网络的卟啉病联盟由这些疾病临床管理方面的专家中心组成，已制定了这些建议。这些建议基于文献、正在进行的自然史研究以及广泛的临床经验。初始评估应包括通过生化检测进行诊断确认、随后进行基因检测以确定具体的急性肝卟啉病，以及完整的病史和体格检查。应向新诊断的患者提供咨询，告知其避免已知的诱发因素。随访频率取决于临床亚组，对可能需要调整治疗的复发性发作患者以及有临床并发症的患者进行密切监测。全面护理应在需要时包括转诊至专科医生。年度评估包括生化检测和对长期并发症的监测。这些指南为监测急性肝卟啉病患者提供了一个框架，以确保获得最佳结果。（《肝脏病学》2017年；66:1314 - 1322）
