Editing Porphyria (section)

==History==
The underlying mechanism was first described by the German physiologist [[Felix Hoppe-Seyler]] in 1871,<ref>{{Cite journal |author=Hoppe-Seyler F |title=Das Hämatin |journal=Tubinger Med-Chem Untersuch |year=1871| volume=4 | pages=523–33}}</ref> and acute porphyrias were described by the Dutch physician [[Barend Joseph Stokvis|Barend Stokvis]] in 1889.<ref name=Lane>{{Cite web |author=Nick Lane |title=Born to the purple: the story of porphyria |work=Scientific American |url=http://www.sciam.com/article.cfm?articleID=000B1BEF-C051-1DF8-9733809EC588EEDF |date=2002-12-16 |access-date=5 August 2008 |url-status=dead |archive-url=https://web.archive.org/web/20071011105238/http://www.sciam.com/article.cfm?articleID=000B1BEF-C051-1DF8-9733809EC588EEDF |archive-date=11 October 2007 |df=dmy-all }}</ref><ref>{{Cite journal |author=Stokvis BJ |title=Over twee zeldzame kleurstoffen in urine van zieken |journal=Nederl Tijdschr Geneeskd | volume=2 | pages=409–417 |language=nl}} Reprinted in {{cite journal | author = Stokvis BJ | title = Over twee zeldzame kleurstoffen in urine van zieken | language = nl | journal = Ned Tijdschr Geneeskd | volume = 133 | issue = 51 | pages = 2562–70 | date = December 1989 | pmid = 2689889 }}</ref>

The links between porphyrias and mental illness have been noted for decades. In the early 1950s, patients with porphyrias (occasionally referred to as "porphyric hemophilia"<ref>Denver, Joness. "An Encyclopaedia of Obscure Medicine". Published by University Books, Inc., 1959.</ref>) and severe symptoms of depression or catatonia were treated with [[Electroshock therapy|electroshock]] therapy.

===Vampires and werewolves===
Porphyria has been suggested as an explanation for the origin of [[vampire]] and [[werewolf]] legends, based upon certain perceived similarities between the condition and the [[folklore]].

In January 1964, L. Illis's 1963 paper 'On Porphyria and the [[Aetiology]] of Werewolves' was published in ''[[Proceedings of the Royal Society of Medicine]]. ''Later, [[Nancy Garden]] argued for a connection between porphyria and the vampire belief in her 1973 book ''Vampires''. In 1985, biochemist [[David Dolphin]]'s paper for the [[American Association for the Advancement of Science]], 'Porphyria, Vampires, and Werewolves: The Aetiology of European Metamorphosis Legends', gained widespread media coverage, popularizing the idea.{{citation needed|date=August 2019}}

The theory has been rejected by a few folklorists and researchers as not accurately describing the characteristics of the original werewolf and vampire legends nor the disease and as potentially stigmatizing people with porphyria.<ref>''American Vampires: Fans, Victims, Practitioners'', Norine Dresser, W. W. Norton & Company, 1989.</ref><ref>[http://www.straightdope.com/columns/read/1321/did-vampires-suffer-from-the-disease-porphyria-or-not "Did vampires suffer from the disease porphyria — or not?"] {{webarchive|url=https://web.archive.org/web/20130205152541/http://www.straightdope.com/columns/read/1321/did-vampires-suffer-from-the-disease-porphyria-or-not |date=5 February 2013 }} [[The Straight Dope]], 7 May 1999.</ref>

A 1995 article from the ''[[Postgraduate Medical Journal]]'' (via [[National Institutes of Health|NIH]]) explains:
<blockquote>As it was believed that the folkloric vampire could move about freely in daylight hours, as opposed to the 20th century variant, congenital erythropoietic porphyria cannot readily explain the folkloric vampire but may be an explanation of the vampire as we know it in the 20th century. In addition, the folkloric vampire, when unearthed, was always described as looking quite healthy ("as they were in life"), whereas owing to disfiguring aspects of the disease sufferers would not have passed the exhumation test. Individuals with congenital erythropoietic porphyria do not crave blood. The enzyme (hematin) necessary to alleviate symptoms is not absorbed intact on oral ingestion, and drinking blood would have no beneficial effect on the sufferer. Finally, and most important, the fact that vampire reports were rampant in the 18th century, and that congenital erythropoietic porphyria is an extremely rare manifestation of a rare disease, makes it an unlikely explanation of the folkloric vampire.<ref>{{cite journal |last=Cox|first=Ann M.|date=1995|title=Porphyria and vampirism: another myth in the making|journal=Postgraduate Medical Journal|volume=71|issue=841|pages=643–644|doi=10.1136/pgmj.71.841.643-a|pmid=7494765|pmc=2398345}}</ref></blockquote>

===Notable cases===
* [[George III of the United Kingdom]]. The mental illness exhibited by George III in the [[Regency Crisis of 1788|regency crisis of 1788]] has inspired several attempts at [[retrospective diagnosis]]. The first, written in 1855, thirty-five years after his death, concluded that he had acute [[mania]]. M. Guttmacher, in 1941, suggested [[Bipolar disorder|manic-depressive]] [[psychosis]] as a more likely diagnosis. The first suggestion that a physical illness was the cause of King George's mental derangement came in 1966, in a paper called "The Insanity of King George III: A Classic Case of Porphyria",<ref>{{cite journal |vauthors=Macalpine I, Hunter R | title = The 'insanity' of King George 3d: a classic case of porphyria | journal = [[Br Med J]] | volume = 1 | issue = 5479 | pages = 65–71 | date = January 1966 | pmid = 5323262 | pmc = 1843211 | doi = 10.1136/bmj.1.5479.65 }}</ref> with a follow-up in 1968, "Porphyria in the Royal Houses of Stuart, Hanover and Prussia".<ref>{{cite journal |vauthors=Macalpine I, Hunter R, Rimington C | title = Porphyria in the royal houses of Stuart, Hanover, and Prussia. A follow-up study of George 3d's illness | journal = Br Med J | volume = 1 | issue = 5583 | pages = 7–18 | date = January 1968 | pmid = 4866084 | pmc = 1984936 | doi = 10.1136/bmj.1.5583.7 }}</ref> The papers, by a mother/son [[psychiatrist]] team, were written as though the case for porphyria had been proven, but the response demonstrated that many experts, including those more intimately familiar with the manifestations of porphyria, were unconvinced. Many psychiatrists disagreed with the diagnosis, suggesting bipolar disorder as far more probable. The theory is treated in ''Purple Secret,''<ref>{{Cite book|author1=Warren, Martin |author2=Rh̲l, John C. G. |author3=Hunt, David C. |title=Purple Secret: Genes, "Madness" and the Royal Houses of Europe |publisher=[[Bantam Books]] |location=London |year=1998 |isbn=978-0-593-04148-2}}</ref> which documents the ultimately unsuccessful search for genetic evidence of porphyria in the remains of royals suspected to have had it.<ref>The authors demonstrated a single point mutation in the [[PPOX gene]] but not one that has been associated with disease.</ref> In 2005, it was suggested that [[arsenic]] (which is known to be porphyrogenic) given to George III with [[antimony]] may have caused his porphyria.<ref>{{cite journal |vauthors=Cox TM, Jack N, Lofthouse S, Watling J, Haines J, Warren MJ | s2cid = 13109527 | title = King George III and porphyria: an elemental hypothesis and investigation | journal = [[The Lancet]] | volume = 366 | issue = 9482 | pages = 332–335 | year = 2005 | pmid = 16039338 | doi = 10.1016/S0140-6736(05)66991-7 }}</ref> This study found high levels of arsenic in King George's hair.  In 2010, one analysis of historical records argued that the porphyria claim was based on spurious and selective interpretation of contemporary medical and historical sources.<ref>{{cite journal |vauthors=Peters TJ, Wilkinson D | s2cid = 22391207 | title = King George III and porphyria: a clinical re-examination of the historical evidence | journal = History of Psychiatry | volume = 21 | issue = 81 Pt 1 | pages = 3–19 | year = 2010 | pmid = 21877427 | doi = 10.1177/0957154X09102616 }}</ref>   The mental illness of George III is the basis of the plot in ''[[The Madness of King George]]'', a 1994 British film based upon the 1991 [[Alan Bennett]] play, ''[[The Madness of George III]]''. The closing credits of the film include the comment that the King's symptoms suggest that he had porphyria, and note that the disease is "periodic, unpredictable, and hereditary". The traditional argument that George III did not have porphyria, but rather bipolar disorder, is thoroughly defended by [[Andrew Roberts, Baron Roberts of Belgravia|Andrew Roberts]] in his new biography ''The Last King of America''.<ref>{{Cite web|url=https://www.amazon.com/Last-King-America-Misunderstood-George-ebook/dp/B08XNB1RYY|title=The Last King of America: The Misunderstood Reign of George III|first=Andrew|last=Roberts|date=9 November 2021|publisher=Viking|via=Amazon}}</ref>
* Descendants of George III. Among other descendants of George III theorized by the authors of ''Purple Secret'' to have had porphyria (based on analysis of their extensive and detailed medical correspondence) were his great-great-granddaughter [[Princess Charlotte of Prussia]] ([[William II, German Emperor|Emperor William II]]'s eldest sister) and her daughter [[Princess Feodora of Saxe-Meiningen]]. They uncovered better evidence that George III's great-great-great-grandson [[Prince William of Gloucester]] was reliably diagnosed with variegate porphyria.<ref>{{Cite book |url=https://books.google.com/books?id=OckqbM7hcGAC&pg=PA21 |title=Tetrapyrroles: Birth, Life and Death |isbn=9780387785189 |last1=Smith |first1=Martin |last2=Smith |first2=Alison |date=2009-12-21 |publisher=Springer |url-status=live |access-date=9 April 2014 |archive-url=https://web.archive.org/web/20140704171216/http://books.google.com/books?id=OckqbM7hcGAC&pg=PA21 |archive-date=4 July 2014 |df=dmy-all }}</ref>
* [[Mary, Queen of Scots]]. It is believed that Mary, Queen of Scots, [[George III|King George III]]'s ancestor, also had acute intermittent porphyria,<ref>{{cite web |last=Röhl |first=John |date=25 June 1999 |title=The Royal Family's Toxic Time-Bomb |url=http://www.sussex.ac.uk/internal/bulletin/archive/25jun99/article1.html |work=Bulletin: The University of Sussex Newsletter |url-status=dead |archive-url=https://web.archive.org/web/20130915114324/http://www.sussex.ac.uk/internal/bulletin/archive/25jun99/article1.html |archive-date=15 September 2013 |df=dmy-all |access-date=18 August 2013}}</ref> although this is subject to much debate. It is assumed she inherited the disorder, if indeed she had it, from her father, [[James V of Scotland]]. Both father and daughter endured well-documented attacks that could fall within the constellation of symptoms of porphyria.{{cn|date=December 2024}}
* [[Maria I of Portugal]]. Maria I—known as Maria the Pious or Maria the Mad because of both her religious fervor and her acute mental illness, which made her incapable of handling state affairs after 1792—is also thought to have had porphyria. [[Francis Willis (physician)|Francis Willis]], the physician who treated George III, was even summoned by the Portuguese court but returned to England after the court limited the treatments he could oversee. Contemporary sources, such as Secretary of State for Foreign Affairs [[Luís Pinto de Sousa Coutinho, 1st Viscount of Balsemão|Luís Pinto de Sousa Coutinho]], noted that the queen had ever-worsening stomach pains and abdominal spasms: hallmarks of porphyria.<ref>{{cite book |last=Roberts |first=Jenifer |date=2009 |title=The Madness of Queen Maria |trans-title=The Remarkable Life of Maria I of Portugal |publisher=Templeton Press |isbn=978-0954558918 }}</ref>
* [[Vincent van Gogh]]. Other commentators have suggested that Vincent van Gogh may have had acute intermittent porphyria.<ref>{{cite journal |vauthors=Loftus LS, Arnold WN | title = Vincent van Gogh's illness: acute intermittent porphyria? | journal = BMJ | volume = 303 | issue = 6817 | pages = 1589–1591 | year = 1991 | pmid = 1773180 | pmc = 1676250 | doi = 10.1136/bmj.303.6817.1589 }}</ref>
* [[Nebuchadnezzar II|King Nebuchadnezzar of Babylon]]. The description of this king in [[Daniel 4]] suggests to some that he had porphyria.{{cn|date=December 2024}}
* Physician [[Archie Cochrane]]. He was born with porphyria, which caused health problems throughout his life.<ref name="outline">{{cite book |last1=Ranpura |first1=Dhruv |title=One Man's Medicine: An Autobiography of Professor Archie Cochrane |last2=Dhyey |first2=Khavdu |publisher=[[HarperCollins]] |year=2009 |isbn=978-0-9540884-3-9 |location=India |language=English |orig-year=1989}}</ref>
* [[Paula Frías Allende]]. The daughter of the Chilean novelist [[Isabel Allende]]. She fell into a porphyria-induced coma in 1991,<ref>{{Cite book |last=Allende |first=Isabel |year=1995 |title=Paula |title-link=Paula (novel) |location=New York |publisher=HarperCollins |isbn=978-0-06-017253-4}}</ref> which inspired Isabel to write the memoir ''[[Paula (novel)|Paula]]'', dedicated to her.

<gallery widths="200px" heights="200px">
File:Allan Ramsay - King George III in coronation robes - Google Art Project.jpg|[[George III of the United Kingdom|George III]] in his coronation robes. [[Coronation Portrait of George III|Portrait]] by [[Allan Ramsay (artist)|Allan Ramsay]], 1762
File:Mary, Queen of Scots after Nicholas Hilliard.jpg|[[Mary, Queen of Scots]] {{circa|1578}}
File:Maria I, Queen of Portugal - Giuseppe Troni, atribuído (Turim, 1739-Lisboa, 1810) - Google Cultural Institute.jpg|[[Maria I of Portugal]] in a {{Circa|1790s}} portrait attributed to [[Giuseppe Troni]] or [[Thomas Hickey (painter)|Thomas Hickey]]
</gallery>

===Uses in literature===
Stated or implied references to porphyria are included in some literature, particularly gothic literature. These include the following:
* The condition is the name of the title character in the gothic poem "[[Porphyria's Lover]]," by [[Robert Browning]].{{cn|date=December 2024}}
* The condition is heavily implied to be the cause of the symptoms suffered by the narrator in the gothic short story "[[Stone Mattress|Lusus Naturae]]," by [[Margaret Atwood]]. Some of the narrator's symptoms resemble those of porphyria, and one passage of the story states that the name of the narrator's disease "had some Ps and Rs in it." {{citation needed|date=January 2022}}