Porphyrias are a group of disorders caused by deficiencies of enzymes (and, in one type, increased activity) involved in the production of heme.
Heme is a chemical compound that contains iron and gives blood its red color. Heme is a key component of several important proteins in the body. One of those proteins is hemoglobin, which enables red blood cells to carry oxygen. Heme is also an important part of certain enzymes made by the liver. Enzymes are proteins produced by cells that speed up chemical reactions in the body.
Heme is produced mainly in the bone marrow and liver through a complex process that requires 8 different enzymes working in concert. The enzymes work one after another in separate steps that take the starting building blocks through several different intermediate compounds, finally producing heme. If there is a deficiency in one of If these enzymes are deficient, or in one type of porphyria (X-linked protoporphyria) the enzyme is too active, certain intermediate compounds (porphyrins and porphyrin precursors) may accumulate. These may accumulate in the
Bone marrow
Liver
Skin
Other tissues
Heme precursors may also appear in excess in the blood or be excreted in the urine or stool. The accumulated heme precursors cause symptoms and can often be detected by testing to help diagnose porphyria. The specific heme precursors that accumulate and the symptoms that develop depend on which enzyme is abnormal.
Porphyrias are a group of different disorders, all of which except one (X-linked protoporphyria) are caused by a deficiency in one of the enzymes needed for heme production. Each enzyme deficiency is caused by an abnormality in the gene (a mutation) responsible for the production of the enzyme in question. The abnormal gene is almost always inherited from one of the parents or, rarely, both. In the case of X-linked protoporphyria, the abnormal gene causes increased activity of an enzyme, resulting in too much of the porphyrin it produces.
Classification of Porphyrias
Porphyrias can be classified in several ways. Classification according to the specific enzyme deficiency is the most accurate.
A simpler classification system distinguishes porphyrias as acute or cutaneous:
Acute porphyrias: Porphyrias that cause abdominal, neurological, and psychiatric symptoms
Cutaneous porphyrias: Porphyrias that cause skin symptoms when the skin is exposed to sunlight
A third classification system is based on where the excess precursors originate:
Hepatic porphyrias: Precursors originate primarily in the liver
Erythropoietic porphyrias: Precursors originate primarily in the bone marrow
Some porphyrias are classified into more than one of these categories.
Acute porphyrias
Acute porphyrias cause intermittent attacks of abdominal, neurological, and psychiatric symptoms. These attacks are typically triggered by prescription medications (including oral contraceptives), alcohol, smoking, and other factors such as fasting, infections, or stress. In young women, hormonal changes during the menstrual cycle are also a typical trigger of acute attacks.
The most common acute porphyria is
Other acute porphyrias include
Variegate porphyria
Hereditary coproporphyria
Delta-aminolevulinic acid dehydratase-deficiency porphyria, which is extremely rare
Some acute porphyrias (variegate porphyria and hereditary coproporphyria) may also cause skin (cutaneous) symptoms.
Cutaneous porphyrias
Cutaneous porphyrias cause symptoms involving the skin after the skin is exposed to sunlight. In these porphyrias, certain porphyrins are deposited in the skin. When exposed to light and oxygen, these porphyrins generate an unstable form of oxygen capable of damaging the skin.
Cutaneous porphyrias cause skin symptoms. These porphyrias include
Porphyria cutanea tarda, the most common cutaneous porphyria
Congenital erythropoietic porphyria
Hepatoerythropoietic porphyria (extremely rare)
Skin becomes fragile and blistered, generally on sun-exposed areas (such as the face, neck, hands, and forearms) or on damaged skin. Identical skin symptoms are also caused by 2 of the acute porphyrias (variegate porphyria and hereditary coproporphyria). Because symptoms take a while to develop after sun exposure, people are often unaware of the connection between their symptoms and sun exposure.
Other cutaneous porphyrias cause symptoms more immediately after a sun exposure. These porphyrias are
People develop a non-blistering, burning pain within minutes or hours after sun exposure. The pain can last for hours or days. The skin often has no change in appearance, but swelling and redness may occur. People with these disorders usually experience early warning symptoms such as tingling or mild burning sensation, called prodromal symptoms, before developing the more severe and persistent skin symptoms. People who experience such warning symptoms should seek shelter from the sun immediately to try to prevent the occurrence of the more severe symptoms.
Diagnosis of Porphyrias
Measuring porphyrins and porphyrin precursors in the urine or blood
Genetic testing
Blood or urine tests
Blood and urine can be tested for porphyrins or their precursor forms. In many of the porphyrias, the urine may take on a red or reddish brown discoloration. Sometimes the discoloration appears only after the urine has stood in air and light for minutes to hours.
Secondary porphyrinuria
Doctors diagnose porphyrias by measuring porphyrins and porphyrin precursors in the urine. However, several diseases unrelated to porphyrias, such as blood disorders or liver disorders, and exposures to certain medications or to toxins such as alcohol, benzene, and lead, may themselves increase the amount of porphyrins in the urine. This phenomenon is described as secondary porphyrinuria. It is a common cause of erroneous over-diagnosis of porphyria.
Screening for Porphyrias
In order to avoid exposure to substances that can precipitate acute porphyria attacks or cutaneous porphyria symptoms, people need to know whether they carry a genetic mutation that leads to a deficient enzyme. Commonly, the genes in a blood or saliva sample are analyzed.
A child whose parent has a known genetic abnormality that can cause an acute porphyria ideally should be tested for presence of the same mutation well before puberty. The child then can learn in advance how to avoid acute attacks, which are rare before puberty.
Older family members of a person with a known genetic abnormality should also be tested to confirm or exclude the possibility that they are predisposed to developing an acute porphyria or could pass the disorder to a child.
More Information
The following English-language resources may be useful. Please note that The Manual is not responsible for the content of these resources.
American Porphyria Foundation: Aims to educate and support patients and families affected by porphyrias and to support research into treatment and prevention of porphyrias
The United Porphyrias Association: Provides education and support to patients and their families; provides reliable information to health-care providers; fosters and supports clinical research to improve diagnosis and management of the porphyrias
International Porphyria Network: Promotes clinical research about porphyrias
The Drug Database for Acute Porphyrias: Provides an up-to-date list of medications available in Europe to assist physicians in prescribing for patients with porphyrias
