Article: Hereditary coproporphyria

What is hereditary coproporphyria?

Hereditary coproporphyria is a rare type of porphyria that can have acute (severe but usually not long-lasting) symptoms along with symptoms that affect the skin. The disorder results from low levels of the enzyme responsible for the sixth step in heme production. Heme is a vital molecule for all of the body's organs. It is a component of hemoglobin, the molecule that carries oxygen in the blood.

Hereditary coproporphyria is a subtype of porphyria.

The signs and symptoms of hereditary coproporphyria are similar to those of acute intermittent porphyria, but attacks of acute symptoms tend to be less severe. Acute attacks usually begin in adulthood and cause abdominal pain, vomiting, diarrhea, and constipation. During an attack, a person may also experience muscle weakness, seizures, and mental changes such as anxiety and hallucinations. These signs and symptoms are triggered by nongenetic factors such as certain drugs, alcohol, dieting or fasting, and certain hormones.

In about 30 percent of people with hereditary coproporphyria, the skin is overly sensitive to sunlight. Exposed areas become fragile and develop blistering and scarring. Skin symptoms may be milder between acute attacks.

A rare form of this disorder called harderoporphyria has severe signs and symptoms that begin in infancy or childhood. In addition to the health problems listed above, children with harderoporphyria experience yellowing of the skin and the whites of the eyes (jaundice) and a low number of red blood cells (anemia).

How common is hereditary coproporphyria?

An estimated 2 per 1 million people are diagnosed with this type of porphyria each year, but the true incidence may be higher because many people with the disorder never experience symptoms. Hereditary coproporphyria has been reported mostly in Europe and North America.

What genes are related to hereditary coproporphyria?

Mutations in the CPOX gene cause hereditary coproporphyria.

The CPOX gene makes an enzyme called coproporphyrinogen oxidase, which is critical to the chemical process that leads to heme production. The activity of this enzyme is reduced by 50 percent in most people with hereditary coproporphyria. In people with the more severe harderoporphyria, the activity of the enzyme is reduced to less than 10 percent of normal. Nongenetic factors such as certain drugs, hormones, and others listed above can increase the demand for heme and the enzymes required to make heme. The combination of this increased demand and reduced activity of coproporphyrinogen oxidase disrupts heme production and allows byproducts of the process to accumulate in the liver, triggering an acute attack.

How do people inherit hereditary coproporphyria?

Hereditary coproporphyria is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to decrease enzyme activity and lead to symptoms. Harderoporphyria results when a person inherits two altered copies of the gene.