A genetic condition that causes victims to crave blood and resemble vampires has been the stuff of myths for centuries. Here’s what science tells us it really is.

When Faust seals his pact with the devil, Goethe lets Mephistopheles state: “Blut ist ein ganz besondrer Saft – Blood is a quite peculiar juice.” With that Faust sells his soul for knowledge and experience previously unattainable to him. Today we know that what makes blood special consists of its components. And if one of those essential components is deficient, people develop a medical condition called porphyria, otherwise known as “Vampire’s Disease”.

To understand porphyria’s cause, let us first review the metabolism of porphyrins. These represent a class of natural compounds, which are made of four connected five-membered ring systems containing nitrogen as heteroatoms and a central metal atom.

Chemical formula of Haem B.

 

Heme, an iron-porphyrin, makes up the non-protein part of hemoglobin that transports oxygen and is responsible for our blood’s red color. During heme’s biosynthesis pyrroles are formed as intermediate products. These nitrogen five-membered heterocycles are the building blocks for porphyrinoid structures, many of which are found in the so-called “pigments of life”.

Eight enzymes facilitate the condensation of pyrrole derivatives and their formation into a macrocycle; followed by iron insertion to get to the final product. Porphryins are built up in body cells to function as prosthetic groups of many globular hemeproteins. All these naturally occurring metalloproteins fulfill various biological tasks. Besides the oxygen-transporting hemoglobin, these other essential pigments include, for example, cytochrome P450s, myoglobin, neuroglobin, catalases, and peroxidases. Enzyme defects in the pathway to heme cause porphyrin precursors being toxically accumulated and excreted by the body. The underlying gene mutations are inherited either in an autosomal or recessive pattern resulting in porphyria.

Incurable and life-altering

Strictly speaking, porphyria describes a group of eight hereditary disorders, which rarely occur, but are incurable and life-altering for patients. Non-genetic causes interrupting various enzymes in the heme pathway are also known for resulting in porphyria-type symptoms, mainly the effects of alcoholism or lead poisoning. Such chemical toxicities can be cured once identified, but any tissue damage cannot be reversed. On the other hand, people that know about their porphyria need to be informed about potential triggers that can cause an attack – a sudden outbreak of the disease that would require immediate medical attention. Among those potential triggers are environmental influences, stress, infections, various chemicals, and drugs.     

Most physicians may never come across such a case throughout their practice. However, diagnostic algorithms for acute and chronic porphyrias exist. These serve as guidance to selecting laboratory tests for differential diagnosis, depending on which symptoms dominate. Clinically, acute symptoms tend to present as diffuse abdominal pain and neurological dysfunctions, whereas photosensitivity corresponds with the chronic form. Standard testing includes biochemical and genetic methods, as well as separation of urine porphyrins using chromatography.

Flow cytometry may be utilized as a detection tool for red blood cell precursors; the technology does not play a role in diagnosing patients routinely. Instead, a qualitative screening known as Watson-Schwartz test can be a quick indicator for a suspected porphyria. The test relies on an Ehrlich reaction to detect porphobilinogen (PBG) in a urine sample, which turns red if PBG is present. The aqueous phase remains colored red even after shaking out with chloroform. Typically, if a result turns out positive, PBG levels are abnormally elevated (usually five times above the reference value).

 

Chemical formula of Porphobilinogen (PGB)

 

In the past the only way porphyria patients could ease their pain was by drinking blood and avoiding sun light. They may also have reacted with high sensitivity to garlic; its sulphur-containing ingredients like diallyl disulphide both inhibit natural heme synthesis and accelerate hemoglobin degradation, which worsen porphyria outbreaks.

Common physical traits of people with porphyria include pale skin, pronounced teeth, and excessive hair growth in the face and next to deformations on the fingers, ears and nose. Early witness reports of people fitting all these descriptions may have fueled the mystery of vampires and werewolves. Those creatures never existed, but victims of porphyria may have served as inspiration for Bram Stoker’s Dracula, which led to cinematic classics like Nosferatu and recent TV shows like HBO’s True Blood series.

Notable individuals impacted by porphyria 

There were always real patients forced to live with their porphyria, even when it was not understood as a disease at all. Famous cases have been linked to porphyria, such as Prince William of Gloucester, a paternal cousin of the present British Queen Elizabeth II. As such he also descended from King George III. Historians long hypothesized that his madness may have been due to an undiagnosed family history of porphyria. However, all available evidence in his case appear not to support such a diagnosis. The ranks of kings and queens suspected of suffering from the same disease are also joined by no other than the brutal ruler of Wallachia, Vlad III, also known as Vlad the Impaler, who earned the sobriquet Dracula. In recent times Paula, daughter of the Chilean novelist’s Isabel Allende, fell into and died from a coma triggered by porphyria, a tragedy prompting her mother to write an autobiographical book about her loss and laments.

Though incurable, porphyrias can be managed. However, they exhibit symptoms that can easily be confused with other disease types, including some autoimmune conditions. Thanks to progress of medical knowledge, porphyria patients can now be evaluated and be given treatment options to avert the stigma associated with it. Clinical scientists should educate primary care physicians on rare medical conditions like human porphyrias. In those cases, laboratory medicine can offer suitable methods to confirm or rule out a diagnosis.

Raising awareness can help to prevent patients showing ambiguous symptoms being misdiagnosed. Gaining knowledge this way means no one needs to sell their soul as Faust did.