Rare Pediatrics News

Disease Profile

Acute intermittent porphyria

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Adolescent

ICD-10

E80.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

AIP; Porphobilinogen deaminase deficiency; PBGD deficiency;

Categories

Congenital and Genetic Diseases; Eye diseases; Kidney and Urinary Diseases;

Summary

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]

Symptoms

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]

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.

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 enzyme/coenzyme activity
0012379
Elevated urinary delta-aminolevulinic acid
0003163
Increased urinary porphobilinogen
0012217
Porphyrinuria
0010473
30%-79% of people have these symptoms
Back pain
0003418
Constipation
0002019
Cranial nerve paralysis
0006824
Hypertension
0000822
Limb pain
0009763
Mental deterioration
Cognitive decline
Cognitive decline, progressive
Intellectual deterioration
Progressive cognitive decline

[ more ]

0001268
Nausea and vomiting
0002017
Neck pain
0030833
Renal insufficiency
Renal failure
Renal failure in adulthood

[ more ]

0000083
Tachycardia
Fast heart rate
Heart racing
Racing heart

[ more ]

0001649
5%-29% of people have these symptoms
Abdominal distention
Abdominal bloating
Abdominal swelling
Belly bloating
Bloating

[ more ]

0003270
Anxiety
Excessive, persistent worry and fear
0000739
Brain imaging abnormality
0410263
Confusion
Disorientation
Easily confused
Mental disorientation

[ more ]

0001289
Dark urine
0040319
Depressivity
Depression
0000716
Diarrhea
Watery stool
0002014
Distal muscle weakness
Weakness of outermost muscles
0002460
Excessive daytime somnolence
Excessive daytime sleepiness
More than typical sleepiness during day

[ more ]

0001262
Fever
0001945
Hallucinations
Hallucination
Sensory hallucination

[ more ]

0000738
Hepatocellular carcinoma
0001402
Hyponatremia
Low blood sodium levels
0002902
Ileus
0002595
Insomnia
Difficulty staying or falling asleep
0100785
Memory impairment
Forgetfulness
Memory loss
Memory problems
Poor memory

[ more ]

0002354
Motor axonal neuropathy
0007002
Motor polyneuropathy
0007178
Paranoia
0011999
Proximal muscle weakness in lower limbs
0008994
Proximal muscle weakness in upper limbs
0008997
Pseudobulbar paralysis
0007024
Respiratory insufficiency
Respiratory impairment
0002093
Respiratory paralysis
0002203
Restlessness
0000711
Seizure
0001250
Sensory impairment
0003474
1%-4% of people have these symptoms
Coma
0001259
Dysuria
Painful or difficult urination
0100518
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased

[ more ]

0000975
Tremor
0001337
Urinary incontinence
Loss of bladder control
0000020
Urinary retention
0000016
Percent of people who have these symptoms is not available through HPO
Acute episodes of neuropathic symptoms
0003489
Autosomal dominant inheritance
0000006
Muscle weakness
Muscular weakness
0001324
Nausea
0002018
Paralytic ileus
0002590
Paresthesia
Pins and needles feeling
Tingling

[ more ]

0003401
Psychotic episodes
0000725
Vomiting
Throwing up
0002013

Cause

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]

Diagnosis

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 enzymeMolecular 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.

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

    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.

    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

      Organizations

      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

            Learn more

            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

            • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
            • Genetics Home Reference (GHR) contains information on Acute intermittent porphyria. This website is maintained by the National Library of Medicine.
            • 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.

                References

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

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