Acute intermittent porphyria

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] 

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]

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] 

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] 

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.

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.

Because porphyria is so rare, few physicians have experience treating patients with the disease. The American Porphyria Foundation (APF) can help individuals with porphyria by putting their doctor's office in touch with a porphyria specialist who can offer guidance on their care. Clinicians and researchers specializing in porphyria are available to consult on suspected or confirmed cases of porphyria, and to discuss the individual course of treatment. Some specialists can assist with diagnostic testing, and some are available for clinical consultation with patients. There is one telemedicine facility for porphyria consultation in the country, at the University of Texas-Medical branch, in Galveston. Patients and physicians interested in utilizing the services mentioned above may call the APF office at 713-266-9617 for information on contacting the specialist who can best address their concerns. More information about this service can be accessed by clicking here. 

Additional researchers and physicians can be found through the Porphyrias Consortium. This resource includes five of the leading porphyria centers in the United States that provide expertise and experience in the diagnosis and treatment of patients with porphyria. The staff in each Center includes porphyria physicians, researchers, research coordinators, and technical/laboratory staff. Together with the American Porphyria Foundation, the Porphyrias Consortium enables a large scale collaborative effort to develop new strategies and methods for diagnosis, treatment, and prevention of illness and disability resulting from these rare disorders. For more information about the Porphyrias Consortium, click here.