A group of eight known blood disorders, known as Porphyria affects body's molecular machinery for making heme. Hemoglobin is the oxygen-transporting protein; heme binds with iron to give the red color. The different genetic variations that affect heme production give rise to different clinical presentations of porphyria.
The most common kind of porphyria, Erythropoietic protoporphyria (EPP) causes skin photosensitive in childhood and results in painful, disfiguring blisters on prolonged exposure to sunshine.
Barry Paw of the Dana-Farber/Boston Children's Cancer and Blood Disorders Center reports, "People with EPP are chronically anemic, which makes them feel very tired and look very pale with increased photosensitivity because they can't come out in the daylight." A slight exposure to UV light causes blistering and disfigurement of the exposed body parts, ears and nose, he says.
Blood transfusions and staying indoors during daylight can alleviate the disease conditions. While in ancient times, the similar effect was achieved by drinking animal blood and emerging only at nights, added facts to the mystery of vampires.
At present, a new genetic mutation that triggers EPP is discovered by Paw and his team. The findings published in the Proceedings of the National Academy of Sciences (PNAS) reveal a novel biological mechanism that identifies the therapeutic target for treating EPP and provide significant evidence for stories of vampires.
Porphyrin synthesis which occurs in the liver and bone marrow leads to heme production. Any genetic defect which affects this process can hamper body’s ability to produce heme. A decreased heme, in turn, leads to accumulation of protoporphyrin components and in case of EPP, protoporphyrin IX accumulates in the RBC’s, plasma and liver. Exposure of protoporphyrin IX to sunlight leads to swelling, burning and redness of the skin.
The genetic pathways leading to accumulation of protoporphyrin IX is explained, but in several cases of EPP, this remains unclear. Paw's team revealed a novel mutation of the gene CLPX involved in mitochondrial protein folding. To show this mechanism, they carry out deep gene sequencing on people with EPP, in which the genetic defect was undefined.
Paw reports that this newly-discovered mutation highlights the complex genetic network that underpins heme metabolism. "Loss-of-function mutations in any number of genes that are part of this network can result in devastating, disfiguring disorders."
Identifying gene mutations contributing to porphyria pave ways for future therapies to treat the related disorders, Paw suggests. "Although vampires aren't real, there is a real need for innovative therapies to improve the lives of people with porphyrias,"
Genetic variations affect heme production and is responsible for the conditions mimicking vampire folklore