Porphyrias are a series of genetically-inherited diseases caused by malfunctions in the body’s production of heme, the molecule used to carry oxygen in the blood. Porphyria comes from the Greek word porphyra, meaning purple pigment, which refers to the purplish glow the urine of porphyria patients emits when exposed to light (Signal, 1993). Porphyrias are generally divided into two classes: erythropoietic and hepatic. Erythropoietic porphyrias are characterized by increased sensitivity to sunlight that causes chronic blistering (Figure 1) (Signal, 1993). Hepatic porphyrias, on the other hand, involve attacks of intense abdominal pain and neurological dysfunction, such as seizures (Signal, 1993). Variegate porphyria (VP) is classified as a hepatic porphyria, however it is unusual in that patients can also exhibit erythropoietic symptoms.
While VP is quite rare, it is most common in South Africa where 1,200/1 million people are diagnosed as opposed to only 7/1 million in Europe (Hift, 2012). The prevalence of VP in South Africa is somewhat coincidental in that it was first brought to the country in 1688 by Dutch settlers of Cape Town. Today, >95% of VP cases in South Africa can be traced back to this original couple (Hift, 2012).
The specific cause of VP is a mutation in the enzyme protoporphyrinogen oxidase (PPOX), which makes protoporphyrinogen IX in the second-to-last step in heme synthesis (Figure 2). This causes heme precursors to accumulate in the body – typically in fat, the liver, and even the brain.
Since VP is so uncommon, diagnosis can be difficult, and genetic testing is often required (Signal, 1993). While the disease can be managed and some treatments are available, no cure has been developed to date. Since VP involves both erythropoietic and hepatic symptoms, care must be taken to handle both aspects of the disease. Blistering that occurs upon exposure to sunlight can be limited by wearing protective clothing and reducing exposure to UV rays (Signal, 1993). Hepatic attacks are often induced by substances such as barbiturates, alcohol, and certain antibiotics; therefore, avoiding these materials is important as well (Signal, 1993). In the event of an attack, patients are often administered glucose and/or hemin intravenously, which work to stop heme synthesis and prevent the accumulation of unused metabolites (Signal, 1993).
Recent advances in VP treatment demonstrate that antioxidants such as vitamins E and C can help reduce the occurrence and severity of hepatic attacks (Ferrer et al. 2013). While this work is a step in the right direction, treatments available for VP remained limited due to its rarity. Therefore, a deeper understanding of the disease is necessary in order to provide better ways for handling it in the clinic.
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