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Overview of Porphyrias

By

Herbert L. Bonkovsky

, MD, Wake Forest University School of Medicine;


Sean R. Rudnick

, MD, Wake Forest University School of Medicine

Last full review/revision Oct 2019| Content last modified Oct 2019
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Porphyrias are a group of disorders caused by deficiencies of enzymes involved in the production of heme.

Heme is a chemical compound that contains iron and gives blood its red color. Heme is the key component of several important proteins in the body. One of the proteins is hemoglobin, which enables red blood cells to carry oxygen. Heme is also an important part of certain enzymes made by the liver.

Heme is produced mainly in the bone marrow and liver through a complex process regulated by eight different enzymes. The enzymes work one after another in separate steps that take the starting compound through several different intermediate compounds (called porphyrins), finally producing heme. The porphyrins themselves are made up of compounds called porphyrin precursors. If there is a deficiency in one of these enzymes, certain 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. The specific heme precursors that accumulate and the symptoms that develop depend on which enzyme is deficient.

Porphyrias are a number of different disorders, each caused by a deficiency in one of the enzymes needed for heme production. Each enzyme deficiency is caused by damage to the gene (a mutation) responsible for the production of the enzyme in question. The damaged gene is almost always inherited from one of the parents or, rarely, both.

Classification

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 neurologic, mental, and abdominal 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, mental, and neurologic symptoms. These attacks are typically triggered by prescription drugs (including oral contraceptives), alcohol, and other factors such as fasting, infections, or stress.

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) 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.

Some cutaneous porphyrias cause symptoms that tend to be continuous or intermittent. These porphyrias include

  • Porphyria cutanea tarda, the most common cutaneous porphyria

  • Congenital erythropoietic porphyria

  • Hepatoerythropoietic porphyria (extremely rare)

People are often unaware of the connection between their symptoms and sun exposure. Their 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 two of the acute porphyrias (variegate porphyria and hereditary coproporphyria).

Other cutaneous porphyrias cause symptoms more immediately after a sun exposure. These porphyrias are

People develop a nonblistering, burning pain within minutes or hours after sun exposure. The pain can last for hours. The skin often has no change in appearance, but swelling and redness may occur.

Diagnosis

  • 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.

Screening

In order to avoid exposure to substances that can precipitate acute porphyria attacks or cutaneous porphyria symptoms, people need to know whether they carry the gene for a deficient enzyme. Commonly, the genes in a blood sample are analyzed.

A child whose parent has an enzyme deficiency that can cause an acute porphyria ideally should be tested 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 an enzyme deficiency should also be tested to confirm or reject the possibility that they are predisposed to developing an acute porphyria or could pass the disorder to a child.

Secondary porphyrinuria

Doctors diagnose porphyrias by measuring porphyrins and porphyrin precursors in the urine. Several diseases unrelated to porphyrias, such as blood disorders, liver disorders, and exposures to toxins such as alcohol, benzene, and lead, may themselves increase the amount of urine porphyrins. This phenomenon is described as secondary porphyrinuria.

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