Porphyria comprises a group of genetic disorders caused by disruptions in the heme production cycle.
Heme is a molecule that enables red blood cells to transport oxygen throughout the body. Composed of iron and protoporphyrin IX, it is built stepwise from porphyrins and their precursors.
When a given step in the heme production pathway is disrupted, porphyrins and other precursor molecules start to accumulate in different tissues and organs, eventually reaching toxic levels. Although this process is most often seen in the kidneys, liver, and skin, it is not limited to these organs. This also lowers the amount of oxygen carried in the blood, leading to some of the disorder’s symptoms.
The loss or dysfunction of a specific enzyme involved in the heme production pathway causes each type of porphyria. The nine different types are grouped into two main classes: acute porphyrias and cutaneous porphyrias.
Acute porphyrias are known for their sudden and sometimes severe attacks that can include neurological and non-neurological symptoms. Acute attacks can also affect the skin, although this is more common in cutaneous porphyrias.
Cutaneous porphyrias are those that mainly affect the skin. In these forms of porphyria, excessive amounts of porphyrins are transported to the skin, where they react with sunlight to produce a range of often painful symptoms.
Mutations in the genes encoding each enzyme involved in heme production underlie each type of porphyria. Simply carrying a mutation, however, does not guarantee that symptoms will develop. Mutations are often seen as predisposing factors, while additional environmental factors are typically needed to trigger the disease. Common environmental factors that may act as triggers for porphyria include heavy alcohol use, sunlight exposure, certain medications and recreational drugs, stress, fasting, and hormonal changes associated with menstruation and menopause.
Porphyria gets its name from urine discoloration, one of the most common symptoms of acute and cutaneous varieties. It comes from “porphura,” an ancient Greek word that means “purple.” A patient’s urine may be purple, red, or brown due to the abnormally high levels of porphyrins and other molecules it contains.
Other symptoms tend to differ between acute and cutaneous porphyrias.
Symptoms of acute attacks often include pain, urinary and gastrointestinal issues, and altered mental status. Skin symptoms are the hallmark characteristic of cutaneous porphyrias. When porphyrins in the skin react with sunlight (and sometimes artificial light), they can damage the surrounding tissues, resulting in painful redness, swelling, itching, burning, and sometimes blisters.
Porphyrias are diagnosed through biochemical tests of blood, urine, or feces, or by genetic testing. The biochemical tests are generally fast, simple, and relatively cheap, but cannot always identify the specific type of porphyria. Genetic testing, on the other hand, is highly sensitive and specific.
Treatment can vary, depending on the type of porphyria and symptom severity. As a first step, it is generally recommended that patients avoid all kinds of environmental triggers that can lead to an attack.
Acute attacks are often treated with injections of hemin and glucose, a simple sugar. The body uses hemin to make heme, which triggers a reduction in porphyrin production when it rises to a sufficiently high level. Glucose provides an easy source of carbohydrates, which helps limit the amount of porphyrins and precursor molecules released by cells — a phenomenon known as the glucose effect.
Recently, Givlaari (givosiran) started being used as a preventive treatment to lower the frequency of acute porphyria attacks.
Treatment for cutaneous porphyrias usually focuses on reducing one’s exposure to sunlight and other possible triggers. Other treatments include drawing blood (phlebotomy) to reduce the amount of circulating iron and porphyrins; administering the anti-malarial agent Plaquenil (hydroxychloroquine), which absorbs excess porphyrins and helps speed their removal from the body; and supplementing with vitamin D to replace what’s lost due to inadequate sun exposure.
Last updated: April 15, 2021
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