Porphyria in the Royal Houses of Stuart, Hanover, and Prussia: A Follow-up Study of George III's Illness

Abstract

It was the purpose of this follow-up study of George s III s illness to raise the diagnosis of porphyria previously made above the uncertainties inherent in posthumous pathography. This was achieved when a living family member was found suffering from it and when in another it was possible to demonstrate the biochemical abnormalities of variegate porphyria by the latest laboratory techniques. Armed with this knowledge we searched George IIPs descendants and ancestry for other cases. Evidence is adduced which suggests that four of his sons and his granddaughter, Princess Charlotte. suffered from it. Among his ancestors and collaterals, through the fortunate survival of informative medical records, the disorder could be traced back to Mary Queen of Scots and her son, James VI of Scotland and I of England. Most remarkable, of him even the repeated passing of the typical port-wine-coloured urine is recorded which the likened to his favourite Alicante wine, still obtainable today. His son, Henry, Prince of Wales, appears to have died in an attack at the age of 18. From James I it must have been transmitted through his daughter, Elizabeth, Queen of Bohemia, to her daughter Sophia, wife of Ernst August, Elector of Hanover. From her, foundress of the English House of Hanover, it must have come down through her son George I to George III and his descendants ; and through her daughter, Sophia Charlotte, wife of Frederick I, King of Prussia, in the Brandenburg-Prussian line to Frederic the Great, cousin-german to George III. The clinical data yet to be gathered from study of this uniquely documented family—spanning 13 generations and more than 400 years—may well add to knowledge of this rare and still incompletely understood disorder. Its dramatic and mysterious features gave rise on five occasions to the suspicion of foul play and created a cause célébre: the illness of Mary Queen of Scots in 1566 ; and the deaths of the Prince of Wales in 1612, of James I in 1625, of Henrietta Anne, Duchess of Orleans, sister of Charles II and sister-in-law of Louis XIV, in 1670, and of Caroline Matilda, hapless Queen of Denmark and Norway, sister of George III, in 1775. The character of some historic figures may now appear in a somewhat different light when their sufferings are seen to have been real and severe, as in the case of Mary Queen of Scots and George IV. Foremost the traditional image of George III, distorted by the false assumption that his illnesses were psychological breakdowns, urgently needs to be looked at afresh. Porphyria may justly be called a royal malady. It caused directly two major national disasters: the Regency Crisis in 1788 when George III had his severest attack, and the catastrophe of 1817 when Princess Charlotte died in childbed with her infant. This tragedy threatened the Hanoverian succession with extinction and left the nation without an heir apparent until the birth in 1819 of Victoria. Porphyria may also have contributed to Queen Anne leaving no heir, a calamity which necessitated safeguarding the Protestant succession by the Act of Settlement of 1701, by which the crown was transferred from the Catholic House of Stuart to that of Hanover, and so brought George I and his descendants to the English throne. © 1968, British Medical Journal Publishing Group. All rights reserved.