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What is porphyria and why is it called “vampire disease”: symptoms and causes

Credit: Rashmi Bhavasar, G Santoshkumar and B Rahul Prakash, CC BY 2.0, via Wikimedia Commons

The news is going around the world: the 32-year-old from Minnesota Phoenix Nightingale claims to have the so-called “vampire disease”for whom she cannot eat garlic because it would be fatal. It’s about the acute intermittent porphyriaa metabolic disorder that belongs to the family of rare hereditary disorders known as porphyrias and caused by deficiencies in the enzymes that synthesize the heme group, a fundamental constituent of hemoglobin. This leads to an accumulation of certain molecules, the porphyrinsresponsible for the serious symptoms associated with these diseases. They cause vomiting, nausea, confusion and skin forms can cause blisters and injuries if you expose your skin to the sun. To date, there is no definitive cure for these diseases. The allergy to light and the connection with blood are the reasons for the name “vampire disease”. So much so that according to some these diseases could be the cause of vampire legendsespecially that of Dracula.

What are porphyrias, rare diseases caused by enzymatic dysfunctions

When we talk about porphyria we are actually talking about a group of 8 hereditary metabolic diseases caused by alterations and dysfunctions of the enzymes that synthesize the heme group. THE’eme it is fundamental for the functioning of the so-called hemoproteins such ashemoglobinin which heme is responsible for binding to oxygen, myoglobin and cytochromes.

hemoglobin heme group
Hemoglobin and heme groups.

In simple words, 8 steps are required to synthesize the heme groupcoordinated by as many enzymes. When one of these enzymes does not work or is deficient not only is less heme produced, but it also causes overproduction and the accumulation of intermediate molecules and heme precursors, le porphyrinswhich end up remaining unused. It is precisely the accumulation of porphyrins at the level of various tissues (bone marrow, liver and skin) that causes the various symptoms of these diseases.

These enzymatic dysfunctions are hereditary and derive from mutations of genes that contain the instructions to “build” the enzymes themselves. The only form that can be acquired, even in the absence of genetic predisposition, is the porphyria cutanea difficileusually caused by iron buildup in the liver, chronic hepatitis C, or excessive alcohol consumption.

Porphyrins also accumulate in the blood, urine and feces. The name of the disease comes from a characteristic of the urine: “porphyria” derives from the Greek πορφυρα, the term to indicate the color viola. If left in the light for a few hours, the porphyrins accumulated in the urine absorb ultraviolet light and the color of the urine changes, going from the classic straw yellow to a purplish red also quite intense.

Urine of a patient with porphyria. Chen GL, Yang DH, Wu JY, Kuo CW, Hsu WH, CC BY 3.0, via Wikimedia Commons
Urine of a patient with porphyria.
Chen GL, Yang DH, Wu JY, Kuo CW, Hsu WH, CC BY 3.0, via Wikimedia Commons

The types and symptoms of porphyrias

Porphyrias are usually classified based on the name of the deficient or malfunctioning enzyme, but it is often more convenient to identify them based on the site where the porphyrins are produced: we will therefore have porphyrias erythropoietic (bone marrow) ed hepatic (liver). Or based on the symptoms, distinguishing between porphyrias acute and chronic (or skin).

Acute porphyrias, such as the acute intermittent porphyria from which Phoenix Nightingale suffers, are characterized by symptoms neurovisceral and are generally hepatic. Attacks usually start out very painful abdominal crampsnausea, vomiting and constipation. In more severe cases, the central and peripheral nervous systems are also affected, with pain in the limbs, mental confusion, convulsions and hallucinations.

Chronic porphyrias can be either hepatic or erythropoietic and are more associated with skin symptoms and photosensitivity. Porphyrins reach the skin through the bloodstream, react with ultraviolet rays and cause abrasionsbubbles, blisterswith skin deformations that negatively influence the quality of life of those affected. In some cases, this phototoxicity is perceived as excruciating pain even without injuries, in others, the abrasions appear already after only 30 minutes of sun exposure.

Why is it called “vampire disease”

From the symptoms described it is easy to understand how the “vampire disease” can be defined and how it has given rise to many myths and legends. The attacks of psychosis that characterized it are also believed to be caused by porphyria the madness of King Georgethe English sovereign of the late eighteenth century. In fact, it is hypothesized that it affected several members of his family (it is, after all, a hereditary disease) and that it was exacerbated by the ingestion of arsenicas reported by a study published in The Lancet.

Heredity is a necessary condition for the development of the disease, but often attacks are triggered by external factorssuch as stress, medications, but also simply from the normal female hormonal cycle. However, the role of another fundamental element of the vampire legend: garlic is not clear. Actually, to date there are no studies which directly link the ingestion of garlic with an aggravation of the symptoms of porphyrias.

Sources

Di Pierro, E., & Granata, F. (2020). Nutrients and Porphyria: An Intriguing Crosstalk. International journal of molecular sciences, 21(10), 3462. Erwin, A. L., & Desnick, R. J. (2019). Congenital erythropoietic porphyria: Recent advances. Molecular genetics and metabolism, 128(3), 288–297. Phillips J.D. (2019). Heme biosynthesis and the porphyrias. Molecular genetics and metabolism, 128(3), 164–177. Murphy GM (1999). The cutaneous porphyrias: a review. The British Photodermatology Group. The British journal of dermatology, 140(4), 573–581. Orphanet: Porphyria