Acute intermittent porphyria

The porphyrias are a group of inherited disorders in which an important constituent of the hemoglobin protein, called the heme group, is not produced properly. The heme group is an iron-containing pigment that is synthesized in our body in a multistep process. Porphyrins are produced when there is a deficiency in any of the enzymes involved in one of these steps, causing abnormal amounts of intermediate precursors, called porphyrins, to accumulate and become toxic.

There are up to seven types of porphyrias, all of which follow an autosomal dominant mode of inheritance, with the exception of Doss porphyria, which is extremely rare and is inherited in an autosomal recessive manner. Here we study acute intermittent porphyria (AIP), which is associated with alterations in the HMBS gene and is the most frequent type of acute porphyria, with a prevalence of 1-2 cases per 15,000 population.

Porphyrias are classified as hepatoid or erythropoietic, depending on the tissue most affected. AIP is hepatoid, the heme precursors accumulate in the liver and can cause neurovisceral seizures. Unlike other porphyrias, AIP does not produce skin symptoms.

The pathogenic variants that cause AIP are said to have low penetrance, meaning that not all people who have a mutation in the HMBS gene develop the peak symptoms of the disease such as neurovisceral seizures, which produce severe abdominal pain usually accompanied by nausea and vomiting;usually accompanied by nausea, tachycardia and hypertension, and neurological and psychiatric symptoms, including behavioral changes, seizures and peripheral neuropathy.

Factors known to trigger seizures in people carrying HMBS mutations include hormonal changes, certain commonly used drugs, stress, alcohol consumption, caloric restriction, and infections that induce overproduction and accumulation of porphyrins in the liver. AIP is associated with long-term complications in the form of primary liver cancer, hypertension and renal failure.

In the treatment of seizures, drugs that can trigger or worsen AIP symptoms should be avoided, appropriate heat supply should be maintained, and infections should be avoided by using appropriate medications. Immediate administration of human hemin (panhematin or hemo arginate) is the specific treatment of choice to stop acute neurovisceral seizures.

Both those who have manifested symptoms of AIP and those who are asymptomatic and are at risk of developing AIP should avoid those factors that may induce seizures (drugs that are not compatible with AIP or illicit drugs, excessive alcohol consumption, alcohol abuse, alcoholism, alcoholism, and other drugs that are not compatible with AIP);cations, excessive alcohol consumption, smoking and severe caloric restriction) and adopt healthy habits such as a balanced diet, prompt treatment of infections and reduction of stress.