National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Acute intermittent porphyria


Other Names:
AIP; Porphobilinogen deaminase deficiency; PBGD deficiency; AIP; Porphobilinogen deaminase deficiency; PBGD deficiency; Uroporphyrinogen synthase deficiency; UPS deficiency; Porphyria, Swedish type; Hydroxymethylbilane synthase deficiency; HMBS deficiency See More
Categories:
This disease is grouped under:
Acute intermittent porphyria (AIP) is one of the liver (hepatic) porphyrias. AIP is caused by low levels of porphobilinogen deaminase (PBGD), an enzyme also often called hydroxymethylbilane synthase. The low levels of PBGD are generally not sufficient to cause symptoms; however, activating factors such as hormones, drugs, and dietary changes may trigger symptoms. Although most individuals with AIP never develop symptoms, symptomatic individuals typically present with abdominal pain with nausea. Treatment is dependent on the symptoms.[1] 
Last updated: 11/11/2015
Some people who inherit the gene for AIP never develop symptoms and are said to have "latent" AIP. Those individuals that present with symptoms usually do so after puberty, probably because of hormonal influences, although other activating factors include: alcohol, drugs (e.g., barbiturates, steroids, sulfa-containing antibiotics), chemicals, smoking, reduced caloric intake, stress, and travel. Symptoms usually last several days, but attacks for which treatment is not received promptly may last weeks or months.[2]

Abdominal pain, which is associated with nausea and can be severe, is the most common symptom and usually the first sign of an attack.[1][2]

Other symptoms may include [1][2]:

• Gastrointestinal issues (e.g., nausea, vomiting, constipation, diarrhea, abdominal distention, ileus)
• Urinary tract issues (e.g., urinary retention, urinary incontinence, or dysuria)
• Neurological issues (e.g., muscle weakness in the arms or legs, paralysis)
• Psychiatric issues (e.g., insomnia, hysteria, anxiety, apathy or depression, phobias, psychosis, agitation, delirium, somnolence, or coma)

Individuals with AIP have an increased risk of developing hepatocellular carcinoma; some develop kidney failure.[2]
Last updated: 11/12/2015

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 40 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain
[ more ] 		0002027
Abnormal urinary color
Abnormal urinary colour
Abnormal urine color
[ more ] 		0012086
Anorexia 0002039
Anxiety
Excessive, persistent worry and fear
0000739
Depressivity
Depression
0000716
Insomnia
Difficulty staying or falling asleep
0100785
Myalgia
Muscle ache
Muscle pain
[ more ] 		0003326
Nausea and vomiting 0002017
Seizure 0001250
Urinary retention 0000016
30%-79% of people have these symptoms
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat
[ more ] 		0011675
Constipation 0002019
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased
[ more ] 		0000975
Hypertensive crisis 0100735
Paresthesia
Pins and needles feeling
Tingling
[ more ] 		0003401
5%-29% of people have these symptoms
Arthralgia
Joint pain
0002829
Cranial nerve paralysis 0006824
Diaphragmatic paralysis
Paralyzed diaphragm
0006597
Hallucinations
Hallucination
Sensory hallucination
[ more ] 		0000738
Hepatocellular carcinoma 0001402
Hyperlipidemia
Elevated lipids in blood
0003077
Hyponatremia
Low blood sodium levels
0002902
Lethargy 0001254
Paraparesis
Partial paralysis of legs
0002385
Renal insufficiency
Renal failure
Renal failure in adulthood
[ more ] 		0000083
Weight loss 0001824
Percent of people who have these symptoms is not available through HPO
Acute episodes of neuropathic symptoms 0003489
Autosomal dominant inheritance 0000006
Diarrhea
Watery stool
0002014
Dysuria
Painful or difficult urination
0100518
Elevated urinary delta-aminolevulinic acid 0003163
Hypertension 0000822
Muscle weakness
Muscular weakness
0001324
Nausea 0002018
Paralytic ileus 0002590
Psychotic episodes 0000725
Respiratory paralysis 0002203
Tachycardia
Fast heart rate
Heart racing
Racing heart
[ more ] 		0001649
Urinary incontinence
Loss of bladder control
0000020
Vomiting
Throwing up
0002013
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Last updated: 7/1/2020
AIP is caused by the deficiency of an enzyme called porphobilinogen deaminase (PBGD), also known as hydroxymethylbilane synthase (HMBS) and formerly known as uroporphyrinogen I-synthase.[1] The deficiency of PBGD is caused by a mutation in the HMBS gene. The HMBS gene is the only gene known to be associated with AIP.[2] However, the deficiency of PBGD alone is not enough to cause AIP. Other activating factors (e.g., hormones, drugs, dietary changes) must also be present.[1] 
Last updated: 11/12/2015
AIP is inherited in an autosomal dominant fashion, which means only one of the two HMBS genes needs to have a disease-causing mutation to decrease enzyme activity and cause symptoms.[2] 
Last updated: 11/12/2015
Diagnosis of AIP is suspected in individuals with otherwise unexplained severe, acute abdominal pain without physical signs.[2] The finding of increased levels of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) in urine establishes that one of the acute porphyrias is present. If PBGD is deficient in normal red blod cells, the diagnosis of AIP is established.[1] The diagnosis is confirmed in individuals with a disease-causing mutation in the HMBS gene, the only gene known to be associated with AIP, which encodes the erythrocyte hydroxymethylbilane synthase enzyme. Molecular genetic testing of the HMBS gene detects more than 98% of affected individuals and is available in clinical laboratories.[2] To obtain a list of clinical laboratories offering genetic testing for AIP, click here.
Last updated: 11/12/2015

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Treatment of AIP may vary based on the trigger of the attack and the symptoms present. Treatment may include stopping medications that cause or worsen the symptoms, treating any infections which may be present, administration of pain medication, monitoring fluid balance and/or correcting electrolyte disturbances, monitoring neurologic status and administering respiratory support. Mild attacks can be manged with increased caloric intake and fluid replacement. Recurrent acute attacks should be managed by a porphyria specialist.[2] Hospitalization is often necessary.[1]  Panhematin, an intravenous medication used to correct heme deficiency, may also be prescribed.[3] More detailed information about the use of Panhematin for the treatment of AIP can be found by clicking here.
Last updated: 11/11/2015

Management Guidelines

  • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.  
  • The American Porphyria Foundation offers a document that includes information about porphyria, types, testing, and treatment with Panhematin®.  Click the "document" link above to view these guidelines.

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

  • Hemin (Brand name: Panhematin) - Manufactured by Abbott Laboratories
    FDA-approved indication: Amelioration of recurrent attacks of acute intermittent porphyria (AIP) temporarily related to the menstrual cycle in susceptible women and similar symptoms which occur in other patients with AIP, porphyria variegata and hereditary coproporphyria.
    National Library of Medicine Drug Information Portal

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses with other acute hepatic porphyrias is dependent on the concentration of porphrins in urine and, particularly, in stools and plasma.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Acute intermittent porphyria. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

  • The Porphyrias Consortium is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with this condition through research. The Porphyrias Consortium has a registry for patients who wish to be contacted about clinical research opportunities.

    For more information on the registry see: https://www.rarediseasesnetwork.org/cms/porphyrias/registry

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Social Networking Websites

  • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

Organizations Providing General Support

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

  • The HealthWell Foundation provides financial assistance for underinsured patients living with chronic and life-altering conditions. They offer help with drug copayments, deductibles, and health insurance premiums for patients with specific diseases. The disease fund status can change over time, so you may need to check back if funds are not currently available.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Acute intermittent porphyria. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Acute intermittent porphyria. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • Can you provide me with general information about acute intermittent porphyria? How can I find a researcher or physician who is knowledgeable about this condition? See answer

  • My child may be at risk to develop acute intermittent porphyria due to a history of the disease on his father's side of the family. Is it possible for an individual with the mutation causing this condition to be asymptomatic? How old must one be in order to be tested? See answer

  • I was recently diagnosed with acute intermittent porphyria. I would like to learn more about this condition. I was also informed some time ago that the porphyrias can be disabling. What information can you provide? See answer

  • My daughter may have acute intermittent porphyria. How is this condition diagnosed? See answer

  • What can you tell me about acute intermittent porphyria and Chester porphyria? See answer


  1. Acute Intermittent Porphyria (AIP). American Porphyria Foundation. 2015; http://www.porphyriafoundation.com/about-porphyria/types-of-porphyria/AIP. Accessed 11/11/2015.
  2. Whatley SD, Badminton MN. Acute Intermittent Porphyria. GeneReviews. February 2013; http://www.ncbi.nlm.nih.gov/books/NBK1193/. Accessed 11/11/2015.
  3. Treatment Options. American Porphyria Foundation. 2015; http://www.porphyriafoundation.com/treatment. Accessed 11/11/2015.