Skip to main content

Hereditary Coproporphyria

What is Hereditary Coproporphyria (HCP)?

HCP is an inherited genetic condition in the heme biosynthesis pathway but it is rarer than AIP. In HCP, the gene responsible is CPOX which produces the enzyme coproporphyinogen oxidase. Defects in coproporphyrinogen oxidase puts the body, and the liver specifically, at risk for abnormal accumulation of porphyrin precursors ALA and PBG which can cause symptoms indistinguishable from acute attacks of AIP. However, the acute attacks can be milder in people with HCP when compared to AIP. Patients with HCP have the same slight increased risk of liver cancer that AIP patients have. As in AIP, >90% of patients with HCP mutations will not develop symptoms.

Unlike AIP, other porphyrins which are sensitive to sunlight exposure also accumulate in HCP. This is why people with HCP can also have blistering skin lesions on sun exposed areas. The blistering is typically on the back of the hands and face.

How is Hereditary Coproporphyria diagnosed?

As with AIP, there are two things to consider when it comes to HCP diagnosis: 1) who is at risk for developing acute attacks of HCP and 2) who is experiencing acute attacks. Genetic testing is used to determine who is at risk for acute attacks and biochemical testing is used to determine who is experiencing symptoms from acute attacks.

  • Biochemical: Acute attacks of HCP are due to abnormally high levels of ALA and PBG, which cause damage to nerves in the body. These two “biomarkers” can be accurately measured in the urine. It is best to take samples during an acute attack (e.g. when someone is having abdominal pain, etc), when the levels of both ALA and PBG should be very high (>5X normal). In patients who experience only one or a few attacks in their lifetime, ALA and PBG levels may be normal outside of attack periods. However, in patients who experience frequent, recurrent acute attacks, ALA and PBG levels are usually elevated even in between attacks.

To distinguish HCP from AIP it is useful to also check the different types of porphyrins in the urine. Elevated porphyrins (not the porphyrin precursors ALA and PBG) are responsible for the blistering skin lesions in HCP. Porphyrins in the blood and stool should also be measured. Please note that slight elevations in porphyrins, particularly in the urine is seen in a number of conditions other than porphyria and is not diagnostic.

  • Genetic: A blood sample is used to look at a person’s genes and whether mutations exist that can cause disease in specific genes. The gene that causes HCP is called CPOX. People who have disease-causing mutations in the CPOX gene are at risk for developing acute attacks, though more than 90% of mutation carriers will never experience acute attacks of HCP. If a patient has a mutation, their immediate family members should be tested for that same mutation as well. This includes their parents, their siblings, and any children they may have. This will allow all family members to receive appropriate care and counseling. Because of this, genetic testing is recommended for patients who already have the diagnosis confirmed with very high ALA and PBG levels.

What are treatments for Hereditary Coproporphyria?

The treatments and preventive measures are the same as in AIP. In addition, patients with blistering from sun exposure will need to protect themselves from sunlight.

How is HCP Inherited?

HCP is an autosomal dominant condition. Autosomal means that the defect is not on the chromosomes that determine sex, and dominant means that you only need to inherit one mutated gene to manifest the disease. The gene that causes HCP is called CPOX.

Most HCP patients have one mutated copy and one normal copy. It is random which of these two copies are inherited, so this means that each child of an HCP patient will have a 50% chance of inheriting the mutated copy and 50% chance of inheriting the working copy.