Acute Intermittent Porphyria (AIP)

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AIP is caused by changes in the HMBS gene, which controls the HMBS enzyme in the heme pathway. Without enough of this enzyme, there is a buildup of compounds called ALA and PBG. These compounds can lead to episodes called acute attacks. Most people (>90%) with changes in the HMBS gene never develop acute attacks.

Acute attacks usually include severe abdominal pain as the main symptom, and can also include weakness, nausea, vomiting, constipation, confusion, restlessness, hallucination, and seizures. There can be other symptoms as well. These attacks can be triggered by certain factors like medications (e.g. barbiturates, sulfonamide antibiotics, anti-seizure drugs, and oral contraceptives), alcohol, dieting, infections, and others. Some people with AIP have few attacks in their life-time, and others can have many attacks. Some women can develop acute attacks around their menstrual cycle. 

Acute attacks are more common in women compared to men, and are rare in children. Most people present with symptoms after puberty, in their 20s-30s. 

Description

Long-term, patients with AIP may have an increased risk of developing high blood pressure, chronic kidney disease and kidney failure, and also have an increased risk of developing liver cancer, called hepatocellular carcinoma.

Treatments

During an attack, patients may often need to be hospitalized. This will allow them to receive medications to handle their pain and fluids if they are unable to stop vomiting or are too nauseated to eat. Panhematin is an FDA approved medication which can help decrease the severity and length of the attack, and is more effective the earlier it is received. Panhematin is administered as an infusion once a day for several days to treat an acute attack. Givlaari is a new treatment for people who have frequent attacks to try and prevent them. In very severe cases liver transplant may be considered. 

Management

• Pain Management
  Acute attacks can be very severe requiring strong pain medications to help relieve the pain. These are generally given during hospitalization. Some people may develop chronic symptoms including chronic pain and should consult with a pain specialist.
• Things to monitor long-term
  People with AIP, even those who do not have acute attacks, should see a porphyria specialist at least once a year for regular follow-up to monitor for the long-term complications. People who have frequent attacks may need to see a specialist more regularly.
• Medications
  Avoiding known triggers of acute attacks is important. There is an online drug database to check which medications may be unsafe for people with AIP.
• Nutrition
  People with AIP should avoid dieting or fasting, and maintain a healthy, balanced diet.

Inheritance

AIP is an autosomal dominant condition. Autosomal means that the defect is not on the chromosomes that determine sex, and dominant means that you only need to inherit one changed gene to have the disease. 

Most AIP patients have one changed copy of the HMBS gene and one normal copy. It is random which of these two copies are inherited. Each child of someone with AIP will have a 50% chance of inheriting the changed copy and 50% chance of inheriting the normal copy. 

There is an extremely rare form of AIP that can happen when someone has two changed copies of the HMBS gene. This form is called “Homozygous AIP” and usually presents in early childhood with serious neurological symptoms like seizures.