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Variegate Porphyria

What is Variegate Porphyria (VP)?

VP is an inherited genetic condition with similar clinical signs and symptoms as AIP, but is rarer than AIP. VP is especially common in South African individuals of Dutch ancestry, where it has been estimated that 3 in 1,000 of the Caucasian population is affected. In VP, the gene responsible is PPOX which produces the enzyme protoporphyrinogen oxidase, Defects in protoporphyrinogen 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 VP when compared to AIP. Patients with VP have the same slight increased risk of liver cancer that AIP patients have. As in AIP, >90% of patients with VP mutations will not develop symptoms.

Unlike AIP, other porphyrins which are sensitive to sunlight exposure also accumulate in VP. This is why people with VP can also have blistering skin lesions on sun exposed areas. The blistering is typically on the back of the hands and face. The occurrence of blistering skin lesions are much more common in VP than in HCP and are not easily treated. The only effective preventive measure is use of protective clothing and avoidance of prolonged sun exposure.

How is Variegate Porphyria diagnosed?

As with AIP, there are two things to consider when it comes to VP diagnosis: 1) who is at risk for developing acute attacks of VP 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 VP 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 VP 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 VP. 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 VP is called PPOX. People who have disease-causing mutations in the PPOX gene are at risk for developing acute attacks, though more than 90% of mutation carriers will never experience acute attacks of VP. 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 Variegate Porphyria?

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 by using sun protective clothing and avoiding prolonged sun exposure.

How is Variegate Porphyria Inherited?

VP 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 VP is called PPOX.

Most VP 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 VP patient will have a 50% chance of inheriting the mutated copy and 50% chance of inheriting the working copy.