What is Hereditary Coproporphyria (HCP)?
HCP is an autosomal dominant disorder caused by mutations in the CPOX gene. These mutations reduce the function of an enzyme called coproporphyrinogen oxidase, which is needed for heme production. Without enough of this enzyme, the body can’t properly convert the chemical coproporphyrinogen into protoporphyrinogen, an essential step in making heme. Certain triggers, such as some medications, fasting, hormonal changes, infections, or stress increase the activity of ALA synthase-1, the first enzyme in the heme production pathway in the liver. This puts extra demand on the deficient CPOX enzyme. As a result, ALA, PBG, and porphyrins build up, leading to nerve damage and other manifestations of an acute attack.
The symptoms of an acute attack in HCP are similar to those in acute intermittent porphyria (AIP). However, attacks in HCP are often milder than those in AIP. One key difference is that HCP occasionally causes skin fragility and blisters with sun exposure, while AIP does not. This happens because porphyrins, in addition to PBG and ALA build up more in HCP than in AIP. These porphyrins are sensitive to sunlight and can lead to skin damage.
Patients with HCP, like AIP patients, face an increased risk of chronic kidney disease and liver cancer.
Most people with a CPOX mutation never experience an acute attack or other symptoms, suggesting that other unknown factors contribute to disease development. Symptoms develop most commonly in menstruating people with disease onset after puberty.
How is Hereditary Coproporphyria diagnosed?
Acute porphyrias, including HCP, are diagnosed using biochemical testing, starting with a urine test to measure porphyrin precursors and porphyrins. This is best done during symptoms, because results may be normal between attacks. A spot urine sample rather than a 24-hour urine sample is recommended. The levels of urinary ALA and PBG during an attack are expected to be markedly elevated. Porphyrins are also elevated, but this finding is not specific for an acute porphyria. Additional blood, urine and stool tests are needed to help determine the specific type of acute porphyria.
Genetic testing can confirm the specific type of porphyria, but it does not replace biochemical testing, which is needed to determine whether the disease might be active and causing symptoms.
Family members of individuals diagnosed with acute porphyria may benefit from testing to see if they have inherited the same mutation. Decisions regarding such testing should consider personal preferences with guidance from a provider with expertise in the porphyrias or genetics.
What are treatments for Hereditary Coproporphyria?
For a patient with a confirmed diagnosis of HCP, a spot urine test measuring porphobilinogen (PBG) can help determine whether they are currently experiencing an acute attack. If the PBG level is normal, an acute attack is unlikely.
The treatments and preventive measures are the same as in AIP. People with blistering from sun exposure should also take steps to protect their skin 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.