What is Porphyria?

Porphyria (pronounced poor-FEAR-ee-uh) is a family of rare, inherited metabolic disorders that affect the nervous system or skin. Porphyrias are predominantly caused by a genetic mutation in one of the eight liver enzymes responsible for the synthesis of heme, an essential component of hemoglobin, the oxygen-carrying compound in red blood cells.[1],[2]

Porphyrias that affect the nervous system are known as acute porphyrias.[1] Acute hepatic porphyrias, or AHP, are a subset of porphyrias that result in a decrease in the amount of heme and a build-up of substances involved in making heme.[3]Because these substances are toxic to the nervous system, patients with AHP can experience painful, incapacitating attacks that involve the nervous system.[2] These attacks can severely impact a patient’s quality of life and can lead to frequent hospitalizations with potentially fatal consequences.[4],[2]

The most common and severe form of AHP is called acute intermittent porphyria or AIP. This ultra-rare inherited disease is caused by mutations in a specific enzyme involved in the production of heme, known as porphobilinogen deaminase, or PBGD.[5] One in 20,000 people has AIP.[5]

Symptoms are Severe and Debilitating

Patients with AHP can suffer from acute and/or recurrent attacks in which symptoms come and go. Attacks are often triggered by exposure to certain factors, such as drugs, dieting or hormonal changes, and last about one to two weeks. Attacks vary by individual and usually first occur between ages 20 and 30.[2] In the United States and Europe, approximately 5,000 people suffer acute attacks annually, and approximately 1,000 of those experience recurrent, debilitating attacks.[5]

The most commonly reported symptoms of an acute attack are:[1]

  • Severe abdominal pain
  • Back or limb pain
  • Nausea and vomiting
  • Peripheral and autonomic neuropathy
  • Urine that is reddish in color
  • Neuropsychiatric symptoms, including paralysis, seizures and confusion
  • Elevated heart rate

There has also been increasing recognition that AHP patients have significant chronic disease manifestations. Natural history studies done both in the US and in Sweden in AIP patients determined that 18 to 22% of AIP patients experience chronic symptoms, most commonly pain (in the abdomen, back or limbs) and fatigue.[6] In 2016, data from an ongoing natural history study sponsored by Alnylam Pharmaceuticals, Inc., conducted in a severely affected AHP patient population with recurrent attacks (quantified as three or more attacks within 12 months of screening), showed that 64% of patients experienced chronic symptoms, with almost 50% experiencing symptoms on a daily basis, most commonly pain, followed by fatigue and nausea.[7]

People suffering from AHP often require recurrent hospitalizations to treat their acute attacks.[2]The 2016 ongoing natural history analysis sponsored by Alnylam found that AHP patients require almost four overnight hospitalizations per year for an avgerage legnth of stay of almost seven days each.[7] During severe attacks, patients with AHP can experience respiratory failure, coma and death.[8] Because the symptoms of AHP can be so severe, many patients experience long-term consequences, such as chronic pain and chronic renal failure [9]

A Correct Diagnosis is Essential

Accurate and early diagnosis of AHP is critical because a delay in diagnosis can lead to a delay in appropriate treatment, which may be life-threatening. However, misdiagnosis and delayed diagnosis are common because symptoms are often associated with other, more common diseases.[10] A recent study of U.S. patients with genetically confirmed acute porphyria found the diagnosis was delayed by an average of 15 years from the onset of symptoms.[1]

A diagnosis is typically confirmed with blood and urine tests. Family screening is essential to identify those who may be at risk for attacks before symptoms occur.[2]


Currently, there are limited treatment options available for AHP; one such option is heme derived from human blood, which is administered intravenously through a large vein or central line.[11]

In some patients who are not responsive to therapy, liver transplantation has been shown to be successful in relieving symptoms. This option is typically used only for patients with severe recurrent attacks.[6]

Novel therapeutics are currently being evaluated for AIP and other types of acute hepatic porphyrias.

For information on ongoing clinical trials, please visit clinicaltrials.gov.

Patient Stories
To better understand the tremendous impact that AHP has on the lives of patients, check out this video highlighting Colin and Rose’s experiences.

  • [1] Bissell DM, Wang B. Acute hepatic porphyria. Journal of Clinical and Translational Hepatology. 2015;3(1):17-26.
  • [2] Puy, Hervé et al. Porphyrias. The Lancet , 2013; 375;9718: 924 – 937.
  • [3] Shoolingin-Jordan PM et al. 5-Aminolevulinic acid synthase: mechanism, mutations and medicine. https://www.ncbi.nlm.nih.gov/pubmed/12686158. Accessed November 9, 2016.
  • [4] American Porphyria Foundation. Acute Intermittent Porphyria (AIP). http://www.porphyriafoundation.com/about-porphyria/types-of-porphyria/AIP. Accessed Aoril 4, 2017.
  • [5] American Porphyria Foundation. Acute Intermittent Porphyria (AIP). http://www.porphyriafoundation.com/about-porphyria. Accessed April 4, 2017.
  • [6] Andersson, C., E. Innala, et al. (2003). “Acute intermittent porphyria in women: clinical expression,use and experience of exogenous sex hormones. A population-based study in northern Sweden.” Journal of Internal Medicine 254: 176-183.
  • [7] Anderson, K. E., M. Balwani, et al. (2016). EXPLORE: A prospective, multinational natural history study of acute hepatic porphyria patients with recurrent attacks. Poster session at American Association for the Study of Liver Diseases: Liver Meeting, Boston, MA USA.
  • [8] Mehta, M. et al. Intensive care management of patients with acute intermittent porphyria: Clinical report of four cases and review of literature. Indian J Crit Care Med. 2010 Apr-Jun; 14(2): 88–91.
  • [9] Pischik, E., Kauppinen, R. An update of clinical management of acute intermittent porphyria. The Application of Clinical Genetics. 2015; 8: 201–214.
  • [10] Liu YP, Lien WC, Fang CC, Lai TI, Chen WJ, Wang HP. ED presentation of acute porphyria. Am J Emerg Med. 2005;23:164–167. doi: 10.1016/j.ajem.2004.03.013.[11] Balwani M; Desnick R.The porphyrias: advances in diagnosis and treatment. Blood. 2012;120: 4496-4504