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The Genetics of Acute Hepatic Porphyria and Emerging Molecular Therapies for Clinical Management


  • Matthew Fabbro School of Medicine, Trinity College Dublin


Acute hepatic porphyria (AHP) is a disease process resulting from a defect in the heme production pathway in the liver. Symptoms are due to the buildup of porphyrin precursors, which contributes to the damage of a variety of organ systems. There are different types of AHP depending on which enzymatic gene is affected and to what extent. The disease typically presents with nonspecific symptoms, so a high degree of suspicion is usually required to make the diagnosis of AHP. The current standard of management typically involves the avoidance of precipitating factors and acute attacks are mainly managed with supportive treatment and administration of intravenous hemin. However, new molecular therapies are emerging, which are demonstrating efficacy in decreasing the frequency and severity of symptomatic attacks by downregulating inappropriately expressed genes using siRNA or replacing deficient proteins by introducing mRNA. This paper explores the pathophysiology, diagnosis, and management of AHP and highlights emerging therapies designed to combat this disease process.


AHP, Genetics, Molecular Therapy


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Working Paper