A recently discovered mutation is helping fill in some of the missing details on a painful disease that some believe explains the mythical creatures of darkness – vampires.

Knowing which genes can give rise to a blood condition known as porphyria could offer clues on how to treat its symptoms or even prevent it from developing in the first place, helping those who are otherwise forced to spend their lives out of the reach of sunlight.

Porphyria describes a range of medical conditions defined by an interruption to the production of haemoglobin – the chemical that gives red blood cells their rich crimson hue and carries oxygen around the body.

Depending on where the production process is interrupted, there can be any number of different symptoms.

One famous sufferer was the "mad" British monarch, King George III, whose acute intermittent porphyria was responsible for his debilitating bouts of abdominal pain and difficulty urinating, if not his poor mental health.

Those with erythropoietic protoporphyria (EPP) also suffer pain, but for rather different reasons – their skin blisters when exposed to sunlight.

Many of the missing steps in the haemoglobin production process have already been traced to specific genes, but there are still cases of the condition which lack a clear genetic cause.

Researchers from the Dana-Farber/Boston Children's Cancer and Blood Disorders Centre have added one more mutation to the books with the discovery of a broken gene that usually plays a key role in changing the structure of proteins in the cell's mitochondria.

"This newly-discovered mutation really highlights the complex genetic network that underpins haem metabolism," says researcher Barry Paw.

Haem is made up of a charged iron atom planted in the middle of a circular organic molecule called a porphyrin. The molecule is produced through a chain of steps involving a sequence of enzymes.

In most people with EPP, an enzyme called ferrochelatase is faulty, meaning they can't take the final step in haem's construction.

But it's now clear some with the condition have a deficiency at the front of the production line. A gene labelled ClpX kicks off the production of haem by activating an important enzyme called δ-aminolevulinate synthase (ALAS).

At least one working copy of ClpX could be just enough to give red blood cells some of the haemoglobin necessary to cart oxygen around the body. But just one isn't enough to keep up to speed, leaving plenty of porphyrin components to pile up in red blood cells.

One such component, protoporphrin IX, has a rather nasty characteristic as it comes close to the skin. It easily soaks up light energy, which it then passes onto oxygen to create what are called reactive oxygen species.

En masse, these can really mess things up by destroying cell structures. Cell damage in those with elevated protoporphrin IX levels leaves them with unsightly, painful skin blisters - a symptom of porphyria.

To avoid suffering the consequences of this photosensitivity, those with the disease tend to either cover up or avoid going near bright light altogether. They also receive frequent blood transfusions to help clear the protoporphrin build-up and treat the aenemia.

Add to that the fact they're already barely making enough haemoglobin to begin with and some darkly familiar characteristics start to emerge.

"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," says Paw.

"Even on a cloudy day, there's enough ultraviolet light to cause blistering and disfigurement of the exposed body parts, ears and nose."

Undead bloodsuckers are no doubt relics of ancient folktales, but medical historians have speculated that those with pale skin that blisters on exposure to sunlight could have helped inspire historical legends of vampires and werewolves.

Whether or not there is any truth to the suggestion, there's little doubt that those with the condition have long suffered both the stigma of disease and the discomfort of its symptoms.

"Although vampires aren't real, there is a real need for innovative therapies to improve the lives of people with porphyrias," says Paw.

Currently those with EPP have few options, aside from reducing the severity of symptoms by managing their lifestyle.

One day gene therapy could lead to a better way to treat these kinds of conditions. Which makes studies like this one all the more important. 

This research was published in PNAS.