Porphyria is named from the ancient Greek word porphura, meaning purple. The Greeks borrowed the term from the Phoenicians, who extracted a purple pigment from purpura mollusks to dye the garments of their royal family. Later, in the Byzantine Empire, the term porphyrogenitos, or "born to the purple," literally meant that the imperial heir was born after the father¿s accession to the throne, in a palace room draped in the color.
However, those with the misfortune to be born to the purple involved in porphyria--a group of diseases that result from abnormal accumulations of red and purple pigments produced by the body, called porphyrins--receive far less than royal treatment. There are at least eight types of porphyria, which vary substantially in their symptoms and severity. Historical victims of the worst, most disfiguring forms may have inspired tales of werewolves and vampires. Even today, managing the disease can be challenging.
Hippocrates is often cited as the first to recognize porphyria (which was then referred to as blood/liver disease) but the causal role of porphyrin pigments was only established in 1871 by the great German pioneer of biochemistry Felix Hoppe-Seyer. In 1889, Dr. B.J. Stokvis described the clinical syndrome as "porphyria," and from then on more and more forms of the syndrome were discovered.
All the versions of porphyria have one thing in common: they each result from faults in the body¿s heme-building machinery. Heme, a component of the oxygen transporter hemoglobin, is made in a sequence of eight steps, as in a factory assembly line. Each step is catalyzed by a separate enzyme. If any of these eight steps fails because of an inherited genetic mutation or an environmental toxin, then the whole assembly line gets jammed. The products of the earlier steps, porphyrin intermediates, may build up to toxic levels. These porphyrins accumulate in the skin and other organs before being excreted in feces and urine (which may turn a port-wine color). Exposed to light, the porphyrins can turn caustic and destroy surrounding tissue.
(Put to medical use, drugs containing porphyrins can attack tumors and other ailments. Unlike most natural porphyrins [but like chlorophyll] these drugs are not purple but green, as they have been modified chemically so that they absorb light at wavelengths that can penetrate into biological tissues. See "New Light on Medicine," by Nick Lane; Scientific American, January 2003.)
Exactly which porphyrins accumulate depends on the site of the jam, and it is this that gives porphyria such a wide range of symptoms. The severity of the jam also varies. In some cases the jam is total, preventing any heme synthesis at all. In others, it is only partial, permitting limited heme synthesis. The blockage of the assembly line also means that the body cannot make enough heme to produce normal red blood cells. Some of these abnormal red cells rupture, leading to hemolytic anemia, while the spleen detects abnormalities in other red cells and breaks them down, making matters worse.
Werewolves and Vampires
One of the more common types of the disease is acute intermittent porphyria (AIP), which famously afflicted the unfortunate King George III of Britain--the "mad king" of Alan Bennett¿s play. In AIP the most notable symptoms are neurological attacks, such as trances, seizures and hallucinations, which often persist over days or even weeks. Luckily, most people with AIP have a latent form, and never develop any symptoms.
Another relatively common form is porphyria cutanea tardea, which presents a very different spectrum of symptoms. In this case, the hallmark is photosensitivity (an excessive reaction to light), which causes chronic blistering and even burns on sun-exposed areas. Healing is slow and is associated with scarring and hair growth, especially on the face. Most of the time the facial hairs are fine, so the hirsutism is barely noticeable. Sometimes, however, the hair growth can give the appearance of a werewolf, leading to speculations that the myths may have had a medical basis.