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Genetic and Rare Diseases Information Center (GARD)

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Acute intermittent porphyria

Other Names for this Disease
  • AIP
  • HMBS deficiency
  • Hydroxymethylbilane synthase deficiency
  • PBGD deficiency
  • Porphobilinogen deaminase deficiency
More Names
Related Diseases
More Related Diseases
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Your Question

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?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is acute intermittent porphyria (AIP)?

Acute intermittent porphyria (AIP) is one of the liver (hepatic) porphyrias. AIP is caused by low levels of porphobilinogen deaminase (PGBD), an enzyme also often called hydroxymethylbilane synthase. The low levels of PGBD 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. Treatment is dependent on the symptoms.[1] 
Last updated: 10/23/2009

What are the symptoms of acute intermittent porphyria (AIP)?

Some people who inherit the gene for AIP never develop symptoms and are said to have "latent" AIP.[2]  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).[2] Symptoms usually last several days, but attacks for which treatment is not received promptly may last weeks or months.[2]

Abdominal pain, which 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., 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.[1]
Last updated: 6/27/2011

Is it possible for an individual who has the disease-causing mutation for acute intermittent porphyria (AIP) to remain asymptomatic? 

Some people who inherit the gene for AIP never develop symptoms and are said to have "latent" AIP.[2]
Last updated: 8/28/2009

What causes acute intermittent porphyria (AIP)?

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. The deficiency of PBGD is caused by a disease-causing mutation in the HMBS gene.  The HMBS gene is the only gene known to be associated with AIP.[1]
Last updated: 10/23/2009

How is acute intermittent porphyria (AIP) inherited?

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: 10/23/2009

Can asymptomatic individuals be tested for acute intermittent porphyria (AIP)?

Testing of at-risk asymptomatic adults for AIP is available using either assay of erythrocyte HMBS enzyme activity or, if the mutation is known in an affected family member, molecular genetic testing of the HMBS gene. Such testing is not useful in predicting whether individuals who inherit an HMBS mutation will be symptomatic, or if they are, the age of onset, severity, or type of symptoms. Before testing at-risk individuals for AIP, it is necessary to first test an affected family member to confirm that the disorder in the family is actually AIP.[2]

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: 8/28/2009

How old must one be in order to be tested for acute intermittent porphyria (AIP)?

Although most testing is done in adults, there may be an advantage to testing at-risk asymptomatic individuals prior to puberty, as symptoms most often develop after this age. Identification of individuals at risk for AIP may alter management because avoidance of known risk factors and other measures may be helpful in preventing acute attacks and other symptoms.[2] 
Last updated: 8/28/2009