Porphyrias, a group of eight known blood disorders, affect the body’s molecular machinery for making heme, which is a component of hemoglobin. When heme binds with iron, it gives blood its hallmark red color.

Erythropoietic protoporphyria, the most common kind of porphyria to occur in childhood, causes people’s skin to become very sensitive to light. Prolonged exposure to sunshine can cause painful, disfiguring blisters.

“People with erythropoietic protoporphyria 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,” Dr. Paw explained.

“Even on a cloudy day, there’s enough UV light to cause blistering and disfigurement of the exposed body parts, ears and nose.”

“Staying indoors during the day and receiving blood transfusions containing sufficient heme levels can help alleviate some of the disorder’s symptoms.”

“In ancient times, drinking animal blood and emerging only at night may have achieved a similar effect — adding further fuel to the legend of vampires.”

Now, Dr. Paw and co-authors report a newly discovered genetic mutation that triggers erythropoietic protoporphyria.

It illuminates a novel biological mechanism potentially responsible for stories of ‘vampires’ and identifies a potential therapeutic target for treating this blood disorder.

“To produce heme, the body goes through a process called porphyrin synthesis, which mainly occurs in the liver and bone marrow. Any genetic defects that impact this process can interrupt the body’s ability to produce heme; the decreased heme production leads to a buildup of protoporphyrin components,” the authors explained.

“In the case of erythropoietic protoporphyria, a type of protoporphyrin called protoporphyrin IX accumulates in the red blood cells, plasma and sometimes the liver.”

“When protoporphyrin IX is exposed to light, it produces chemicals that damage surrounding cells. As a result, people with erythropoietic protoporphyria experience swelling, burning and redness of the skin after exposure to sunlight — even trace amounts of sunlight that pass through window glass.”

“Some genetic pathways leading to build-up of protoporphyrin IX have already been described, but many cases of erythropoietic protoporphyria remain unexplained.”

By performing deep gene sequencing on members of a family from France with erythropoietic protoporphyria of unknown etiology, the researchers discovered a novel mutation of the gene CLPX, which plays a role in mitochondrial protein folding.

“This newly-discovered mutation really highlights the complex genetic network that underpins heme metabolism,” Dr. Paw said.

“Loss-of-function mutations in any number of genes that are part of this network can result in devastating, disfiguring disorders.”

Source: Sci News