Key Takeaways

  • Diagnosing acute hepatic porphyria (AIP) involves measuring porphobilinogen (PBG) levels in urine during symptomatic episodes, combined with genetic testing to identify HMBS gene alterations that cause enzyme deficiency.
  • Treatment centers on intravenous hemin (Panhematin) infusions to manage acute episodes, while givosiran (Givlaari) injections administered monthly can help prevent future episodes by reducing toxic porphyrin precursor levels.
  • Women receive an AIP diagnosis approximately 1.5 to 2 times more frequently than men, likely related to hormonal fluctuations during the menstrual cycle that can trigger symptoms.

Acute hepatic porphyrias (AHP) are a group of rare, mostly inherited disorders that result from the obstruction of the body’s heme production process. Heme is an important part of hemoglobin, which is essential for carrying oxygen throughout the body. It helps with gas exchange, signal transmission, energy production, and more.

In each type of porphyria, there is a deficiency of a specific enzyme needed for heme production, and when heme production is obstructed, porphyrins or porphyrin precursors build up.

Types of AHP are either acute or cutaneous (affecting the skin).

Acute intermittent porphyria (AIP) is the most common acute porphyria type and the most severe.

AIP is characterized by a deficiency of the enzyme hydroxymethylbilane synthase (HMBS), also known as porphobilinogen deaminase (PBGD), leading to the buildup of toxins in the body.

These toxins, called porphyrin precursors, are compounds called delta-aminolevulinic acid (ALA) and porphobilinogen (PBG), and their accumulation can cause severe, acute episodes.

People with AIP have high porphyrin precursor levels because the body’s heme production is interrupted.

AIP manifests as attacks or episodes, which can include abdominal pain, gastrointestinal symptoms, and nerve symptoms like neuropathy. Sometimes, other symptoms can include:

Unexplained abdominal pain, together with some other symptoms, can raise suspicion of AIP.

Diagnosis of AIP can be tricky because the symptoms occur periodically and can sometimes be nonspecific. Doctors usually diagnose AIP by looking for characteristic symptoms during an episode, reviewing medical history, and performing a clinical exam and lab tests.

Clinical testing may include screening tests to measure PBG levels in urine, as high levels can be associated with AIP episodes. Doctors can also perform genetic testing to identify an HMBS gene alteration, which may prompt other family members to undergo testing.

Doctors diagnose AIP 1.5 to 2 times more often in women than in men. This may be due to the hormones associated with the menstrual cycle.

If other symptoms are characteristic of AIP, a medical professional may consider it a diagnosis.

Outside factors, like medications, alcohol, hormonal changes, or insufficient calorie intake, typically trigger episodes of AIP. The episodes usually last about a week, with symptoms usually presenting as:

  • severe abdominal pain with constipation and vomiting
  • psychiatric symptoms, such as depression
  • peripheral neuropathies, including weakness in the lower extremities
  • central nervous system impairment, such as delirium, weakness progressing to quadriplegia, and difficulty breathing

In between episodes, many people report being symptom-free, but 20% to 64% of people may experience chronic, severe symptoms like pain, nausea, fatigue, and neuropathy.

With treatment, you can manage the condition. But if the AIP does not respond to heme therapy and keeps recurring, the only cure currently available is a liver transplant.

Some medications can trigger AIP, specifically those that encourage heme production in the liver, and it’s important to avoid them. The American Porphyria Foundation (APF) has a searchable drug database in which you can find information on specific medications, but some may include:

  • ketamine
  • erythromycin (Ery-Tab, Erythrocin, E.E.S)
  • nitrofurantoin (Macrobid)
  • spironolactone (Aldactone, CaroSpir)
  • valproic acid (Depakote, Depakene)
  • carbamazepine (Tegretol)
  • risperidone (Risperdal)

Talk with your doctor about the medications to avoid if you have an AIP diagnosis or if you suspect that you might have the condition.

The goal of AIP treatment is to manage symptoms, avoid complications, and manage heme production in the liver.

The preferred treatment for acute AIP episodes is with a hemin (Panhematin) intravenous (IV) infusion. Your healthcare team may also administer IV glucose to help reduce the number of porphyrin precursors.

Some other treatment options might include:

  • pain management
  • stopping medications that may have triggered the episode
  • ensuring you get enough calories and nutrients, especially carbohydrates

In 2019, the Food and Drug Administration (FDA) approved givosiran (Givlaari) for the treatment of AHP. It is a monthly subcutaneous (under the skin) injection that reduces ALA and PBG levels. This may lead to fewer acute AIP episodes.

Different specialists may form the treatment team, collaborating to address all the symptoms. Those specialists can include pediatricians, neurologists, hematologists, and psychiatrists.

While AIP episode severity can differ from person to person, without proper diagnosis and appropriate treatment, complications can become life threatening.

Currently, the only cure for AIP is a liver transplant. This involves removing the diseased liver and replacing it with a healthy liver, or part of one, from a donor. Liver transplants are typically only available in very severe cases where a person’s quality of life is greatly impacted.

A liver transplant has a survival rate of about 80%, but there is a high risk of hepatic artery thrombosis, or blood clots.

AIP is a condition associated with an enzyme deficiency that affects heme production. It causes episodes that may include severe abdominal pain and other varying symptoms.

Without accurate diagnosis and treatment, it can cause severe, even life threatening complications.

However, you can manage the condition, especially if you receive an early diagnosis and prompt treatment.

Treatment usually focuses on relieving specific symptoms, such as pain management, as well as IV heme therapy. While there is currently no cure, a liver transplant may be possible for those with a significantly impaired quality of life.