words by Nisal Karunaratne
When regarding this, there is one disease that comes to mind: Porphyria.
Porphyria is named from the ancient Greek word porphura, meaning ‘purple’. It is a disease caused by the abnormal accumulation of haem precursor molecules called porphyrins. Haem, a key component of haemoglobin is made in a catalytic cycle made of eight steps, each step catalysed by a separate enzyme.
A genetic mutation or an environmental toxin causes the cycle to get jammed, leading to build-up of porphyrin intermediates in the body. The severity of the disease depends on the types of porphyrins and hence a wide range of symptoms, the most common being haemolytic anaemia.
One of the most common types of disease is Acute Intermittent Porphyria, with the most famous sufferer being King George III of Britain. The most notable symptoms include trances, seizures and hallucinations – hence the nickname ‘Mad King George.’
Another common type is Porphyria Cutanea Tarda, with the main hallmark being photosensitivity. The accumulation of porphyrins in skin and the excessive reaction to light often results in skin burns and blistering. Wound healing is also slow, which causes hypertrophic scarring. Another common feature of this disease form is excessive hirsutism, especially on the face. Excessive facial and bodily hair growth may have given the appearance of a werewolf, suggesting that these myths may have a medical basis.
One of the rarer forms of the disease is Congenital Erythropoietic Porphyria (CEP), caused by mutations in the gene encoding the enzyme uroporphyrinogen. Severe symptoms of CEP include light activated photo-mutilation, resulting in facial disfigurement, loss of fingers, hypertrophic scarring, blindness, teeth darkening and abnormal protrusion and discolouration of urine.
Historical victims of the worst, most disfiguring forms may have inspired tales of vampires. It’s well known that this condition was common in the valleys of medieval Transylvania due to incest. Supposedly, the most famous bearer was the 15th century Romanian prince called Vlad III, also known as Vlad the Impaler or Vlad Dracula, ruler of Wallachia (southern Transylvania) known for his victories against Ottoman Empire during the Crusades or the ‘Holy war’. His historical reputation as a brutal and harsh ruler with an apparent ‘taste for blood’ is thought to have inspired Bram Stoker’s 1897 Gothic horror novel ‘Count Dracula’.
Haem infusion helps treatment of porphyria by overcoming haem shortage and suppressing further synthesis of toxic porphyrin intermediates via negative feedback. Interestingly, evidence has shown that the haem pigment can survive digestion and be absorbed intestinally, suggesting that sufferers from medieval times may have drunk blood to help relieve symptoms of porphyria – another possible inspiration for vampire legends and Vlad Dracula. Future therapies include bone-marrow transplantation which has proven to be challenging and therefore used as a last resort. Gene therapy also seems to be promising, which consist of faulty genes being replaced with functional ones using an adenovirus vector.