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REVIEW article

Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1374965

Acute intermittent porphyria: a disease with low penetrance and high heterogeneity

Provisionally accepted
Lei j. jia Lei j. jia 1Shuang Li Shuang Li 1Bai-Xue Dong Bai-Xue Dong 1Jing Yang Jing Yang 2Yi Ren Yi Ren 2*
  • 1 Department of First Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi Province, China
  • 2 Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China

The final, formatted version of the article will be published soon.

    Acute intermittent porphyria (AIP) is caused by mutations in the gene encoding hydroxymethylbilane synthase (HMBS), a key enzyme in the heme biosynthesis pathway. AIP is an autosomal dominant disorder characterized by low penetrance and a highly heterogenous clinical presentation. The estimated prevalence of AIP is 5 -10 cases per 100,000 persons, with acute attacks manifesting in less than 1% of the at-risk population. This low frequency of attacks suggests significant roles for oligogenic inheritance and environmental factors in the pathogenesis of the disease. In recent years, identification of several modifier genes has advanced our understanding of the factors influencing AIP penetrance and disease severity. This review summarizes these factors including the impact of specific HMBS mutations, oligogenic inheritance, mitochondrial DNA copy number, age, sex, the influence of sex hormones, and the role of environmental factors. Further studies into the etiology of AIP disease penetrance should inform pathogenesis, potentially allowing for the development of more precise diagnostic and therapeutic approaches.

    Keywords: Acute intermittent porphyria, Hydroxymethylbilane Synthase, gene mutation, Penetrance, heterogeneity, Oligogenic inheritance

    Received: 23 Jan 2024; Accepted: 29 Jul 2024.

    Copyright: © 2024 jia, Li, Dong, Yang and Ren. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yi Ren, Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China

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