Introduction

Porphyrias are a group of disorders caused by deficiencies of enzymes involved in the production of heme.

Heme, a chemical compound that contains iron and gives blood its red color, is the key component of several important proteins in the body. The essential functions of heme depend on its ability to bind oxygen. Heme is incorporated into hemoglobin, a protein that enables red blood cells to carry oxygen from the lungs to all parts of the body. Heme is also a component of cytochromes (a type of protein). Some cytochromes in the liver process (metabolize) chemicals--including drugs and hormones--so that they are more easily removed from the body.

Heme is produced in the bone marrow and liver through a complex process regulated by eight different enzymes. As this production process progresses, several different intermediate compounds (heme precursors) are created and modified. If there is a deficiency in one of the enzymes that are essential for heme production, certain heme precursors may accumulate in tissues (especially in the bone marrow or liver), appear in excess in the blood, and get excreted in the urine or stool. The specific precursors that accumulate depend on which enzyme is deficient. One group of heme precursors is called the porphyrins.

Porphyrias are a number of different diseases, each caused by a specific abnormality in the heme production process. Most porphyrias are hereditary. All people with a particular porphyria have a deficiency of the same enzyme. The result is a deficiency or inactivity of a specific enzyme in the heme production process, with resulting accumulation of heme precursors.

Some porphyrias result in photosensitivity (extreme sensitivity to sunlight) because certain porphyrins are deposited in the skin. When exposed to light and oxygen, these porphyrins can generate a charged, unstable form of oxygen capable of damaging the skin. Nerve damage, leading to pain and even paralysis, can also occur in some porphyrias. Some porphyrias result in abdominal pain and liver damage.

The three most common porphyrias are porphyria cutanea tarda, acute intermittent porphyria, and erythropoietic protoporphyria. These disorders are very distinct: their symptoms differ considerably, different tests are required for their diagnosis, and different treatments are involved. Some features of these porphyrias are shared with the other, less common forms (which include delta-aminolevulinic acid dehydratase deficiency, congenital erythropoietic porphyria, hepatoerythropoietic porphyria, hereditary coproporphyria, and variegate porphyria).

See the sidebar Classifying Porphyrias.