The porphyrias are a group of rare, genetic disorders. People living with a porphyria have changes to certain genes, called mutations, which affect their body’s ability to regulate itself.
In the porphyrias, these mutations are in the genes involved in a certain chemical pathway, called the heme biosynthetic pathway. Heme is a compound that the body needs to make hemoglobin and there are several steps to make this compound in the body. Each type of porphyria is caused by a defect in a specific enzyme in the heme biosynthetic pathway. Without these enzymes working properly, the body is not able to finish making heme and it causes a buildup of other compounds, called porphyrins. It is the buildup of different types of porphyrins that causes the different types of porphyria and associated symptoms.
Most commonly the porphyrias are divided into the “acute hepatic porphyrias” (AHPs) and “cutaneous porphyrias,” depending on the primary symptoms.
AHPs, including acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), and ALA-dehydratase deficiency porphyria (ALD) typically present with sudden attacks of severe stomach pain, among other symptoms, which last for several days; VP and HCP may also have skin symptoms of blistering after sun exposure.
The cutaneous porphyrias present with blistering and scarring of the skin, pain, and/or redness and swelling in sun-exposed areas.
The porphyrias may also be classified as “hepatic” or “erythropoietic,” depending on the organ where the porphyrins accumulate. This includes the liver for the acute hepatic porphyrias (AIP, HCP, VP, porphyria cutanea tarda (PCT), and hepatoerythropoietic porphyria (HEP) or the bone marrow for the erythropoietic porphyrias (congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP), and X-linked protoporphyria (XLP).