Acute intermittent porphyria and long-term complications

Acute intermittent porphyria (AIP) is the most common type of acute hepatic porphyria in most regions of the world. Like all forms of porphyria, AIP occurs due to an enzyme deficiency that prevents the body from synthesizing heme, an important component of red blood cells. As with other types of acute hepatic porphyrias, the enzyme deficiency that results in AIP occurs in the liver (hepatic meaning “of or relating to the liver”).

With AIP, the body is deficient in the enzyme porphobilinogen deaminase (PBGD), also called hydroxymethylbilane synthase. PBGD is one of eight enzymes needed to complete the synthesis of heme. When there is not enough PBGD (or any of these eight enzymes) the process bottlenecks, leading to an accumulation of heme precursors. These precursors are called porphyrins. Excess amounts of porphyrins are toxic.

People with AIP will experience episodes or attacks where excessive levels of porphyrins disrupt the normal functioning of the nervous system. During an attack, a person can experience a wide range of symptoms, including severe abdominal pain, gastrointestinal distress, and neurological symptoms, including numbness and tingling in the arms and legs, muscle weakness, and loss of motor function. Attacks are potentially life-threatening and require immediate and proper treatment.

Long-term complications

In addition to the symptoms that occur during an attack, AIP can also result in a number of serious long-term complications that develop over a number of years. These include:

• Chronic pain. Gastrointestinal pain, back pain, peripheral neuropathy, and muscle weakness are all possible symptoms during an AIP attack. For some patients, these symptoms become chronic, and persist between attacks. This is thought to be a result of nerve damage from repeated AIP attacks over many years.
• Hypertension. High blood pressure, or hypertension, is common during AIP attacks, and can sometimes become chronic. High blood pressure increases a person’s risk of heart attack, heart failure, stroke, and kidney failure.
• Chronic kidney disease (CKD). The kidneys are a pair of fist-sized organs that filter waste and excess fluid from the blood and produce urine. Repeated attacks of AIP can cause permanent damage to the kidneys. Some people with AIP undergo kidney transplants.
• Liver cancers. Research suggests that people with AIP—as well as other forms of hepatic porphyria—may be at an increased risk of liver cancers, such as hepatocellular carcinoma (HCC). Liver transplants have been used as a treatment in severe and difficult cases of AIP.

Preventing long-term complications

The best way to prevent short-term and long-term complications of AIP is to work with a healthcare provider who understands the condition and can address your needs as a patient. Because porphyrias are rare, it can be difficult to find a clinic or healthcare provider that specializes in the treatment of these disorders. The American Porphyria Foundation recommends that patients work with a primary care physician who coordinates with a porphyria specialist while overseeing treatment. Regular appointments with a primary care physician are also important for monitoring blood pressure, kidney function, and the health of your liver.

Treatment for AIP involves avoiding triggers and being prepared for an attack when one occurs. Treatment for an attack will depend on how severe the attack is, but commonly includes high doses of glucose and may include infusions of a therapy called hemin. There is also a preventive medication for acute hepatic porphyrias that was approved by the FDA in 2019.