Acute Intermittent Porphyria's Symptoms and Management: A Narrative Review

Acute intermittent porphyria (AIP) is an autosomal dominant disorder of heme biosynthesis in the liver that is caused by the accumulation of toxic heme metabolites aminolevulinic acid (ALA) and porphobilinogen (PBG) due to a deficiency in the enzyme hydroxymethylbilane synthase (HMBS). The prevalence of AIP is found to commonly affect females of reproductive age (ages 15-50) and people of Northern European descent. The clinical manifestations of AIP include acute and chronic symptoms that can be outlined into three phases: the prodromal phase, the visceral symptom phase, and the neurological phase. Major clinical symptoms involve severe abdominal pain, peripheral neuropathy, autonomic neuropathies, and psychiatric manifestations. Symptoms are often heterogeneous and vague, which can lead to life-threatening signs if not treated and managed appropriately. Whether treating AIP in its acute or chronic form, the cornerstone of treatment consists of the suppression of the production of ALA and PBG. The mainstay of managing acute attacks continues to comprise discontinuing porphyrogenic agents, adequate caloric support, heme treatment, and the treatment of symptoms. In recurrent attacks and chronic management, prevention is key with the consideration of liver transplantation and/or renal transplantation. In recent years, there has been great interest in emerging treatments that focus on a molecular level such as enzyme replacement therapy, ALAS1 gene inhibition, and even liver gene therapy (GT), which has changed the way of traditionally managing this disease and will pave the way for innovative therapies to come.