What Is Porphyria?

Porphyria refers to a group of at least eight disorders that affect the human nervous system and skin. These disorders are usually genetic, but some people with a porphyria may not experience symptoms unless they encounter certain triggers, and others may never experience symptoms at all. It's estimated that about 1 in 25,000 people in the US have porphyria, and there may be as many as 1 in 50 people with porphyria worldwide. Porphyria can be diagnosed with blood, urine, and stool tests, and sometimes with an ultrasound of the abdomen.

Types of Porphyria:

There are two main categories of porphyria: acute porphyrias and cutaneous porphyrias. Acute porphyrias can affect both the nervous system and the skin, while cutaneous porphyrias usually only affect the skin. Two types of porphyria, variegate porphyria and hereditary coproporphyria, are considered both acute and cutaneous porphyrias because they can affect both the nervous system and skin.

Acute Cutaneous Both Acute and Cutaneous

Acute Intermittent Porphyria (AIP) Porphyria Cutanea Tarda (PCT) Variegate Porphyria

ALAD-Deficiency Porphyria (ADP) Erythropoietic Protoporphyria (EPP) Hereditary Coproporphyria

Erythropoietic Protoporphyria (EPP) or Protoporphyria

Hepatoerythropoietic Porphyria (HEP)

Causes of Porphyria:

General Causes:

Porphyria can be caused by inheriting faulty genes from one parent, called autosomal dominant pattern porphyria, or by inheriting faulty genes from both parents, called autosomal recessive pattern porphyria.

Porphyria occurs because too much of a group of chemicals called porphyrins, shown above in gray and blue, builds up in the body. Humans naturally have some porphyrins in their bodies, but they are normally converted into heme, a chemical compound that is found throughout the body. Heme is important because it is a big part of hemoglobin, which is a protein that allows blood to carry oxygen and carbon dioxide throughout the body. In those with porphyria, the body does not produce enough of at least one of the eight enzymes that convert porphyrin into heme, which leads to the build up of porphyrins.

Having a build-up or porphyrins can cause a variety of symptoms, depending on where the build-up occurs. This is why there are multiple types of porphyria. For instance, in PCT, porphyrins build up primarily in the liver, while in HEP, porphyrins build up mostly in red blood cells, blood plasma, and bone marrow.

One type of porphyria, PCT, is typically acquired, rather than inherited, though conditions that predispose a person to PCT do run in families. PCT is a build-up of porphyrins in the liver, which can be caused by a combination of several different things, including too much iron or estrogen in the body, some viruses, and an inherited deficiency of a certain enzyme called uroporphyrinogen decarboxylase (UROD).

Attack triggers:

Even when a person has porphyria, he may not experience symptoms unless there is a trigger; a substance or circumstance that sets off an attack. Common porphyria triggers include:

Hormone fluctuations, particularly those related to estrogen. Many women with porphyria experience attacks before or during menstruation or during pregnancy.
High iron levels.
A virus or infection, like hepatitis.
Using drugs or alcohol, and possibly smoking.
Some over the counter medications, including some birth controls, sedatives, barbiturates, some antibiotics, vitamins, anesthetics, and tranquilizers.

A porphyria attack doesn't always have a known trigger though, which can make it difficult for people with porphyria to know when an attack is coming on or how to prevent them.

Symptoms of Porphyria:

Most people with any kind of porphyria do not develop symptoms. In this case, it is called latent porphyria. When symptoms do occur, they can include:

Extreme photosensitivity, or sensitivity to light. Those with porphyria are often extremely allergic to sunlight, and can develop serious burns and itchy blisters just from walking outside. These burns and blisters are also known as photodermatitis, and often scar.
Urine that turns red or purple in sunlight.
Edema, or water retention, which leads to swelling.

Those with acute porphyrias may experience all of the above symptoms as well as:

Seizures.
Paranoia, confusion, and anxiety.
Hallucinations.
High blood pressure.
Insomnia.
Vomiting, diarrhea, and constipation.
Severe pain in the muscles, stomach, limbs, and back that sometimes leads to weakness.
Excessive sweating, and accompanying dehydration.

Some types of porphyria, particularly acute intermittent porphyria, have symptoms that can come and go suddenly, sometimes without any known trigger. This can make porphyria extremely hard to diagnose, since the tests used for diagnoses work by detecting porphyrin levels, which are particularly elevated right before and during an attack. If a person's levels are relatively normal between attacks, it's hard to make a diagnosis. It usually takes several rounds of tests to diagnose porphyria because of the way it tends to come and go and because many of the symptoms of porphyria are also symptoms of other conditions.

Sometimes other conditions can cause porphyria-like symptoms, including something called pseudoporphyria. People with pseudoporphyria are often sensitive to light and may get itchy blisters when their skin is exposed to light too. Doctors can distinguish between porphyria and pseudoporphyria with a blood or urine test.

Treatments:

The treatments for porphyria usually center around preventing attacks and lowering the body's porphyrin levels. Preventative treatments include:

Identifying and avoiding triggers.
Minimizing stress.
Wearing sunscreen and covering up when going outside.
Taking care of illnesses and infections promptly.
Getting good nutrition and following a high-carbohydrate diet. High carbohydrate levels can limit porphyrin production.

Other treatments focus on lowering porphyrin levels in the body. This can be done either by removing the porphyrins directly, or by trying to make the body produce less porphyrin to begin with. These types of treatments include:

Chloroquine and other anti-malarial drugs. Though these drugs are normally taken to prevent or treat malaria, they can absorb porphyrin and help the body get rid of it more quickly.
Beta carotene supplements. If taken long-term, these supplements may help increase skin's tolerance to light.
Phlebotomy, or drawing blood. This removes iron from the body, which temporarily leads to less porphyrin production.
Intravenous (IV) fluids, particularly sugars and other carbohydrates. This helps limit porphyrin production.
IV heme substitutes like Panhematin®.

Most people with porphyria are also given painkillers during attacks, and psychiatric treatment as needed. As late as the 1950s, porphyria sufferers were treated with electroshock therapy, but it is no longer a recommended treatment.

Porphyria in Culture and History:

People speculate that several well-known historic figures had porphyria, including “Mad” King George III, who was ruling the United Kingdom during the American Revolution. Though this theory was popularized and even included in the movie The Madness of King George, no conclusive evidence has been found. George III's great-great-great-grandson, Prince William of Gloucester, was diagnosed with variegated porphyria in the late 1960s. Other psychiatrists speculate that the painter Vincent van Gogh and his brother might also have had porphyria.

Porphyria has also been offered as an explanation for the development of vampire and werewolf legends, since those with porphyria are sensitive to light, as vampires are said to be, and sometimes suffer mental breakdowns which can lead to irrational behavior, which may have led to them being labeled vampires or werewolves in pre-modern times.

Additional Resources:

Websites:

www.porphyriafoundation.com — Detailed information about the specific types of porphyria as well as treatments and support for porphyria sufferers.

http://emedicine.medscape.com — General information about porphyria and a diagram of heme production.

www.mayoclinic.com — A broad overview of porphyria, including causes, symptoms, and treatments.

http://digestive.niddk.nih.gov — General information about porphyria as well as specific information about the enzymes involved in porphyrin conversion.

www.ncbi.nlm.nih.gov — An overview of causes, symptoms, risk factors, treatments, and complications.

Videos:

Video 1 — Urine from a porphyria sufferer changing colors in the sun.

Video 2 — General information about porphyria and heme conversion.

Video 3 — Further information about porphyria with illustrations.

Written by Niki Foster