PORPHYRIA AND THE VAMPIRE DISEASE
- Ben Levinson
- 5 minutes ago
- 5 min read
By Benjamin Levinson, MD
INTRODUCTION
The term “Vampire” immediately conjures up an image of a person who fears the sun, sleeps in a coffin during the day, and hunts for victims at night to drink their blood. It is quite a story that many have believed over the centuries. It has been recognized that a possible origin for this legend is a disease called porphyria (1).
The term ‘porphyria’ comes from the Greek work ‘purple’ as most people who have this disease see purple in their urine (2). Porphyria actually describes a group of diseases some of which cause skin sensitivity to sunlight leading to the idea of sun avoidance as part of the vampire myth. All of these conditions are related to the formation of hemoglobin, the molecule in blood that carries oxygen to the cells. If there is a failure in the proper formation of hemoglobin, then these conditions occur (1).
HEMOGLOBIN AND PORPHYRIN FORMATION
So how are porphyrins produced? This question can best be addressed by understanding how hemoglobin is formed.
Hemoglobin is synthesized in developing red blood cells. It is composed of four subunits, each containing a protein chain called globin and a non-protein component called heme. The interest here is in the heme part of hemoglobin. This is the place of the porphyrin molecule. The heme portion (Figure 1) is composed of the porphyrin ring and contains an iron atom in the center which is the site where oxygen binds and unbinds (3). Porphyrin synthesis is the process that produces heme (4). Before discussing further, it is important to note that Vitamin B6 and zinc are necessary in the synthesis of porphyrins.
Figure 1: The Heme Molecule
Cellular synthesis involves a multi-step enzymatic pathway. It begins with the formation of a molecule called 5'-aminolevulinic acid (ALA) for which Vitamin B6 is needed. Two of these molecules then combine to form porphobilinogen (PBG). Zinc is needed at this stage. Four molecules of PBG then are combined to form hydroxymethylbilane (HMB). Chemical reactions
on HMB result in uroporphyrinogen III. If this step is not performed correctly, then a porphyria called protoporphyria will result.
The uroporphyrinogen III will then be transformed into coproporphyrinogen III which is then converted into protoporphyrinogen IX and converted to protoporphyrin IX. Then an iron atom is inserted and heme is created.
Quite an amazing process! And, as will be seen, a lot can go wrong, although it rarely does.
PROBLEMS WITH VAMPIRES
Porphyria cutanea tarda: This is the most common type of porphyria. It is due to a deficiency or decreased activity in the enzyme that changes uroporphyrinogen III to produce coproporphyrinogen III. It can be acquired or hereditary. Uroporphyrin accumulates in the urine. Symptoms include photosensitivity leading to blisters developing in sun-exposed areas and hyperpigmentation, and hepatic injury. Treatment includes avoidance of sunlight, hydroxychloroquine, and phlebotomy. It is this avoidance of sunlight that forms the basis of the vampire legend. It is noteworthy, although not fully confirmed in early medical records, that treatment of these patients is by phlebotomy (removal of blood) which further supports the vampire myth.
Erythropoietic porphyria: This occurs due to a deficiency in the enzyme responsible for the final formation of heme in the biosynthesis pathway by combining protoporphyrin IX and iron. Deficiency leads to an accumulation of protoporphyrin IX in erythrocytes. Symptoms include painful photosensitivity- swelling burning and itching in sun-exposed areas, sometimes hepatic dysfunction. Here again the legend of the vampire myth can be seen to originate.
Acute intermittent porphyria is a result of mutation of the enzyme that creates uroporphyrinogen II. This leads to an accumulation of ALA and porphobilinogen. Complaints of severe abdominal pain, vomiting, constipation, abdominal distention, and behavioral changes (irritability, insomnia, emotional lability),(5) hypertension, and tachycardia. Lab results show elevated urinary porphobilinogen and the urine darkens on exposure to air and sunlight. Patients presenting with acute intermittent porphyria are not photosensitive.
Lead Poisoning: Lead interacts with zinc cofactors leading to inhibition of these two enzymes in the biochemical biosynthetic pathway of heme. This inhibition leads to mostly ALA and some protoporphyrin IX accumulating in urine. Symptoms include abdominal pain, vomiting, fatigue irritability and developmental disability in children.
SUNLIGHT SENSITIVITY
There is the question of why the skin of a person who has porphyria cutanea tarda or erythropoietic porphyria reacts to sunlight and not to ordinary electric lights or candles. This is because the porphyrin actually changes chemical structure when it is exposed to a particular
wavelength of light. This wavelength is only found in sunlight. Interestingly, when bilirubin, a byproduct of heme breakdown, is exposed to a given wavelength it will chemically change as well. This is the basis of the phototherapy that is used in excessive jaundice in babies. In this case, the bilirubin concentration is reduced by light and does not cause a cutaneous reaction as with the porphyrias (6).
THE MADNESS OF KING GEORGE
No discussion of porphyria would be complete without mentioning King George the III. It has been hypothesized that King George III had a form of porphyria that left him with mental illness on occasion (7). There is an interesting but poorly documented story that before the American revolution, representatives were sent to England to see if there could be some sort of representation of the colonies in parliament. However, King George was mentally ill at the time and could not see the delegation. They returned home believing that the king did not want to discuss the matter with them. This ‘insult’ was supposedly a contributing factor to the revolution.
Although it was known that King George suffered from a form of porphyria that was genetic and therefore seen in other genetically-related monarchs, it has been alternatively hypothesized that bipolar disorder or even arsenic poisoning was involved.
CONCLUSION
It is hoped that this brief discussion of these very unusual diseases with prompt further interest and research as much needs to be done to understand these illnesses and their treatment.
(4) Ogun AS, Joy NV, Valentine M. Biochemistry, Heme Synthesis. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537329/
(5) Kim HJ, Khalimonchuk O, Smith PM, Winge DR. Structure, function, and assembly of heme centers in mitochondrial respiratory complexes. Biochim Biophys Acta. 2012 Sep;1823(9):1604-16
(6) Wang J, Guo G, Li A, Cai WQ, Wang X. Challenges of phototherapy for neonatal hyperbilirubinemia (Review). Exp Ther Med. 2021 Mar;21(3):231. doi: 10.3892/etm.2021.9662. Epub 2021 Jan 20. PMID: 33613704; PMCID: PMC7859475.
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