de Souza Paulo Victor Sgobbi, Badia Bruno de Mattos Lombardi, Farias Igor Braga, Pinto Wladimir Bocca Vieira de Rezende, Oliveira Acary Souza Bulle
Division of Neuromuscular Diseases, Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
Front Neurosci. 2021 Sep 27;15:715523. doi: 10.3389/fnins.2021.715523. eCollection 2021.
Acute hepatic porphyria represents a rare, underdiagnosed group of inherited metabolic disorders due to hereditary defects of heme group biosynthesis pathway. Most patients have their definite diagnosis after several years of complex and disabling clinical manifestations and commonly after life-threatening acute neurovisceral episodes or severe motor handicap. Many key studies in the last two decades have been performed and led to the discovery of novel possible diagnostic and prognostic biomarkers and to the development of new therapeutic purposes, including small interfering RNA-based therapy, specifically driven to inhibit selectively delta-aminolevulinic acid synthase production and decrease the recurrence number of severe acute presentation for most patients. Several distinct mechanisms have been identified to contribute to the several neuromuscular signs and symptoms. This review article aims to present the current knowledge regarding the main pathophysiological mechanisms involved with the acute and chronic presentation of acute hepatic porphyria and to highlight the relevance of such content for clinical practice and in decision making about therapeutic options.
急性肝卟啉病是一组罕见的、诊断不足的遗传性代谢紊乱疾病，由血红素生物合成途径的遗传性缺陷引起。大多数患者在出现数年复杂且致残的临床表现后，通常是在经历危及生命的急性神经内脏发作或严重运动障碍后才得到明确诊断。过去二十年进行了许多关键研究，发现了新的可能的诊断和预后生物标志物，并开发了新的治疗方法，包括基于小干扰RNA的疗法，该疗法专门用于选择性抑制δ-氨基乙酰丙酸合酶的产生，并减少大多数患者严重急性发作的复发次数。已确定几种不同的机制导致了多种神经肌肉体征和症状。这篇综述文章旨在介绍目前关于急性肝卟啉病急性和慢性表现所涉及的主要病理生理机制的知识，并强调这些内容在临床实践以及治疗选择决策中的相关性。
