Arbella Stuart: Porphyria in the Royal Family

In 1966, King George III was posthumously diagnosed as suffering from porphyria, a genetically transmitted condition. The suggestion of porphyria as the root cause of George’s ‘madness’ was first put forward in 1966 by Macalpine and Hunter.[1] They suggested that he suffered from acute intermittent porphyria, a diagnosis that they later updated to one of variegate porphyria. This analysis was popularised by the Alan Bennett play, The Madness of King George. In Macalpine and Hunt’s follow-up work, George III and the Mad Business, they suggested that there was a strong possibility that Arbella Stuart also suffered from porphyria. This, they claimed, would explain sudden illnesses, that seemed to come and go and were thought to be feigned, the colicky pains, the severe abdominal pains, and bouts of what seemed to her contemporaries to be mental derangement – evidence of which can certainly be seen in the some of her letters, which are verbose, disorganised, and hard to understand, compared with her normal clear style.

This idea of porphyria was expanded significantly in Rohl and Warren’s 1998 book, Purple Secret: Genes, Madness, and the Royal House of Europe, who traced the disease’s descent to George III from Mary, Queen of Scots, who exhibited many of what have come to be seen as the classic symptoms of the disease.[2] Mary and Arbella’s joint ancestor was Margaret Tudor, daughter of Henry VII and Elizabeth of York, and wife of James IV of Scotland. Margaret herself often suffered from ill-health, but to my knowledge, has never been identified as having porphyria. Assuming it was not a spontaneous genetic malfunction in Margaret, she would have needed to inherit the gene from her parents – which might also lead to investigations into the not dissimilar symptoms that both Mary I and Elizabeth I exhibited under times of stress – severe stomach-aches, swellings, illnesses that came and went suddenly.

The possibility of Arbella suffering from porphyria is discussed by Sara Jane Steen in her edited collection of Arbella’s letters, is at the core of Ruth Norrington’s 2002 biography, In the Shadow of the Throne and is considered by Gristwood in Arbella, England’s Lost Queen. Gristwood is not so didactic as Norrington, but thinks it probable that Arbella did suffer from porphyria. Such a diagnosis makes Arbella’s story even more tragic, and also helps explain some of her behaviour, which can appear erratic.

There is just one problem. In 2011, an article in the Journal of Clinical Pathology, proved (so far as can be proved for people long-dead) that George III did not have porphyria. Porphyria is a genetically-linked disease, which can be inherited from either parent, but which does not necessarily manifest itself in observable symptoms. It is estimated that the gene prevalence of variegate porphyria is 7 individuals per million in Europe and the UK, with around 40% of those carrying the gene manifesting symptoms.[3] Based on these figures, Hift et al concluded that amongst the nine hundred (as at 2011) or so descendants of George III and his siblings not one has been confirmed as having variegate porphyria and only ten have presented symptoms that might be the disease. Consequently, it is statistically impossible that George had the illness. More likely diagnoses for George III have been given as bipolar disorder and dementia.

This debunking of the theory continued in 2012, when the diagnosis of Mary, Queen of Scots, as having porphyria was criticised by C W Sies, C M Florkowski, and L S Pike, in a letter to the academic journal, Clinical Chemistry. They cited the Hift paper, and added a possible diagnosis for James VI and I (who had also been identified as a possible porphyria sufferer) might be Lesch-Nyhan syndrome.[4] Another fascinating paper analysed the letters James wrote in the period 1604 to 1624 identify a reduction in cognitive ability following the reported illness of 1618 – 1619.[5] This contributed to a possible diagnosis of vascular dementia.

That George III did not have porphyria does not, of course, completely negate the possibility that Mary, Queen of Scots, and Arbella Stuart had the disease, but looking at the statistics cited by Hift, it does seem extremely unlikely. Perhaps we should not ascribe Arbella’s health problems and fits of apparent mental disturbance as anything beyond what might be expected to manifest in an intelligent, articulate woman whose royal blood meant that she was educated to be a queen, but was denied not only the fulfilment of that training, but even the most basic control of her own life.

[1] I. Macalpine and R. Hunter, ‘The “Insanity” of King George 3d: A Classic Case of Porphyria.’, Br Med J, 1.5479 (1966), 65–71 <https://doi.org/10.1136/bmj.1.5479.65>.

[2] John C. G. Röhl, Martin Warren, and David Hunt, Purple Secret: Genes, ‘madness’ and the Royal Houses of Europe (London: Bantam, 1998).

[3] Richard J. Hift, Timothy J. Peters, and Peter N. Meissner, ‘A Review of the Clinical Presentation, Natural History and Inheritance of Variegate Porphyria: Its Implausibility as the Source of the “Royal Malady”’, Journal of Clinical Pathology, 65.3 (2012), 200–205 <https://doi.org/10.1136/jclinpath-2011-200276>.

[4] P. Garrard and others, ‘Attenuated Variants of Lesch-Nyhan Disease: The Case of King James VI/I’, Brain, 133.11 (2010), e153–e153 <https://doi.org/10.1093/brain/awq156>.ac

[5] K. Williams and others, ‘Written Language Clues to Cognitive Changes of Aging: An Analysis of the Letters of King James VI/I’, The Journals of Gerontology Series B: Psychological Sciences and Social Sciences, 58.1 (2003), P42–44 <https://doi.org/10.1093/geronb/58.1.P42>.