Acute Intermittent Porphyria (AIP)

How AIP works

AIP is the most common of the acute forms of porphyria. Heme is made in a chain of 8 enzyme steps, mainly in the bone marrow and liver. In AIP, the third enzyme (porphobilinogen deaminase, also called hydroxymethylbilane synthase) works at about half its normal level. Under normal conditions this is enough. When the liver is pushed to make more heme, for example by certain drugs or hormones, two precursors called delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) pile up. ALA is toxic to nerves, which explains the symptoms.

AIP is inherited in an autosomal dominant pattern: a person with one altered gene has a 50% chance of passing it to each child. However, most gene carriers (estimates range widely, but the large majority) never have symptoms.

Symptoms of an AIP attack

Attacks develop over hours to days and can last days to weeks.

• Abdominal pain: severe, diffuse and poorly localized, often with a soft belly on examination. This occurs in almost all attacks.
• Nausea, vomiting and constipation
• Dark or reddish-brown urine that may darken further when left standing in light
• Fast heart rate and high blood pressure
• Pain in the back, arms or legs
• Muscle weakness, starting in the arms and legs, which can progress to paralysis and breathing failure, sometimes mistaken for Guillain-Barré syndrome
• Anxiety, insomnia, confusion, hallucinations
• Seizures, sometimes caused by low sodium (hyponatremia)

Unlike some other porphyrias, AIP does not cause skin blistering from sunlight.

Triggers

• Medicines: barbiturates, some anti-seizure drugs (phenytoin, carbamazepine), sulfonamide antibiotics, some hormonal contraceptives, rifampin, and others. Safe-drug databases list which medicines are safe.
• Hormones: the luteal phase of the menstrual cycle (before periods), progesterone.
• Fasting and low-calorie diets, including after surgery or illness.
• Alcohol and smoking.
• Infections, surgery and stress.

Diagnosis

AIP is often missed for years because symptoms resemble common abdominal problems. The key test is:

• Urine porphobilinogen (PBG): a spot urine sample taken during symptoms. A markedly raised level confirms an acute porphyria attack. This test is quick and should be done in anyone with unexplained severe abdominal pain plus nerve or psychiatric symptoms.

Additional tests:

• urine ALA and porphyrins, and blood and stool porphyrins, to identify the type of porphyria
• blood sodium, kidney and liver function
• genetic testing to confirm the specific gene change and test relatives

Treatment of an acute attack

1. Stop all trigger medicines and treat infections.
2. IV hemin (hemin for injection), given daily for about 4 days. It switches off the liver's overproduction of ALA and PBG and is the most effective treatment.
3. Glucose (carbohydrate) loading by mouth or IV, which also suppresses the pathway; used for mild attacks or while hemin is obtained.
4. Pain control: opioids are generally considered safe for AIP pain.
5. Anti-nausea medicines that are safe in porphyria.
6. Treatment of fast heart rate and high blood pressure, often with beta-blockers.
7. Correcting low sodium carefully.
8. Monitoring breathing in severe weakness.

Long-term management

• Avoid triggers: check every new medicine against a porphyria drug database, avoid alcohol and smoking, and do not fast or crash diet.
• Givosiran: a monthly injection that reduces the liver enzyme driving the pathway. It is approved for adults with acute hepatic porphyria and significantly reduces attack frequency.
• Hormone suppression: for attacks tied to the menstrual cycle, under specialist care.
• Medical alert ID and an emergency care letter.
• Liver transplant for rare, severe, frequent attacks not controlled by other treatments.

Complications

• chronic nerve damage (peripheral neuropathy) and persistent weakness
• chronic pain
• high blood pressure and chronic kidney disease
• increased risk of liver cancer (hepatocellular carcinoma), so people with symptomatic AIP are usually offered regular liver ultrasound from about age 50

Outlook

With early diagnosis, trigger avoidance and prompt treatment, most people have few attacks and live normal lives. Repeated or untreated severe attacks can cause lasting nerve damage.

Frequently asked questions

What are the symptoms of acute intermittent porphyria?

The main symptom is severe abdominal pain, often with vomiting, constipation, a fast heart rate, high blood pressure and dark or reddish urine. Attacks can also cause muscle weakness, anxiety, confusion, hallucinations and seizures.

What triggers an AIP attack?

Common triggers include certain medicines, menstrual-cycle hormones, fasting or dieting, alcohol, smoking, infections, surgery and stress. People with AIP should check new medicines against a porphyria drug safety list.

Does porphyria change urine color?

Yes. During an attack urine often looks dark, reddish or brown, and may darken further when left in light. Normal-colored urine does not rule it out; a urine PBG test is needed.

Is acute intermittent porphyria hereditary?

Yes. It is inherited in an autosomal dominant way, so each child of a carrier has a 50% chance of inheriting the gene change. Most carriers never have symptoms, but relatives should be tested so they can avoid triggers.