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

Abstract

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.

Acute intermittent porphyria complicated with acute pancreatitis: A case report and literature review

“…Among these subtypes, AIP is the most common. [7] AIP is a rare autosomal dominant genetic disease characterized by recurrent acute onset. AIP attacks can be triggered by various factors such as surgery, certain medications, radiation exposure, pregnancy, menstruation, infection, and fasting.…”

The Hepatic Porphyrias: Revealing the Complexities of a Rare Disease

“…100 Intravenous Hemin-The Current Standard of Care Seizures and motor neuropathy suggest acute neurovisceral attacks which can be severe and require hospitalization; these and other acute symptoms require treatment with intravenous hemin infusions and are best managed in the intensive care unit. 102 Treatment with hemin can also prevent frequent noncyclical attacks. 66,103 Infusion with hemin and glucose restores the hepatic heme pool, and initiates the inhibitory feedback mechanism on hepatic ALAS; this in turn reduces heme precursor production and excretion.…”

A novel mutation c.457C > T p.Q153 in the HMBS gene in a Mexican woman with acute intermittent porphyria

“…This deficiency leads to the accumulation of toxic heme metabolites, namely aminolevulinic acid (ALA), and porphobilinogen (PBG) 1 . The precise mechanisms through which porphyrin precursors trigger the symptoms of AIP are not fully understood 1,2 …”

“…Preliminary assessment for AIP involves the detection of markedly elevated porphyrin levels in urinary, stool or serum during an acute attack, followed by subsequent genetic analysis to confirm the presence of HMBS gene mutations 4 . The management of AIP encompasses a comprehensive approach that includes the management of acute attacks, prevention of future episodes, long‐term monitoring, and the treatment of associated complications 2 …”

“…1 The precise mechanisms through which porphyrin precursors trigger the symptoms of AIP are not fully understood. 1,2 AIP presents with a range of clinical manifestations that can be categorized into three distinct phases: the prodromal phase, the visceral symptom phase, and the neurological phase. Prominent clinical symptoms include the occurrence of acute neurovisceral episodes, marked by intense abdominal pain, mental disturbances, and heightened sympathetic activity.…”