Acute hepatic porphyrias for the neurologist: current concepts and perspectives

ABSTRACT Background: Acute hepatic porphyrias represent an expanding group of complex inherited metabolic disorders due to inborn errors of metabolism involving heme biosynthesis. Objective: We aimed to review the main clinical and therapeutic aspects associated with acute hepatic porphyrias. Methods: The authors provided a wide non-systematic review of current concepts and recently acquired knowledge about acute hepatic porphyrias. Results: Acute neurovisceral attacks are the most common and life-threatening presentation of this group and are often considered the main clinical manifestation by clinicians during differential diagnosis and the start of proper diagnostic work-up for acute porphyrias. However, atypical presentations with central nervous system involvement, neuropsychiatric disturbances, and some subtypes with photosensitivity usually make the definite diagnosis difficult and late. Early therapeutic interventions are essential during emergency treatment and intercritical periods to avoid recurrent severe presentations. The availability of new disease-modifying therapeutic proposals based on small interfering RNA (siRNA)-based therapies, complementary to the classic intravenous glucose infusion and hemin-based treatments, emphasizes the importance of early diagnosis and genetic counseling of patients. Conclusions: This review article highlights the main biochemical, pathophysiological, clinical, and therapeutic aspects of acute hepatic porphyrias in clinical practice.

【背景】急性肝卟啉病（acute hepatic porphyrias）是一类不断扩大的复杂遗传性代谢疾病群，其病因涉及血红素生物合成通路的先天性代谢缺陷。【目的】本研究旨在综述急性肝卟啉病相关的主要临床与治疗学要点。【方法】作者针对急性肝卟啉病的现有认知及最新研究成果，开展了大范围的非系统性综述。【结果】神经内脏发作是该类疾病最常见且危及生命的临床表现，临床医师在鉴别诊断及启动急性卟啉病的规范诊断流程时，通常将其视为核心临床表型。然而，伴随中枢神经系统受累、神经精神异常的非典型临床表现，以及部分亚型出现的光敏性，往往会导致明确诊断困难且延误诊治。在急诊治疗与缓解间期及时开展治疗干预，是避免疾病复发出现重症表现的关键。基于小干扰RNA（small interfering RNA, siRNA）的新型疾病修饰治疗方案，可作为经典静脉葡萄糖输注与血红素类治疗的补充手段，其临床应用进一步凸显了对患者开展早期诊断与遗传咨询的重要性。【结论】本综述着重阐述了临床实践中急性肝卟啉病的核心生化、病理生理、临床及治疗学要点。