King George III and porphyria: an elemental hypothesis and investigation

@article{Cox2005KingGI,
  title={King George III and porphyria: an elemental hypothesis and investigation},
  author={T. Cox and N. Jack and S. Lofthouse and J. Watling and J. Haines and M. Warren},
  journal={The Lancet},
  year={2005},
  volume={366},
  pages={332-335}
}
In 1969 it was proposed that the episodic madness suffered by King George III (1738-1820) resulted from an acute hereditary porphyria, variegate porphyria, caused by deficiency of protoporphyrinogen oxidase. The diagnosis was based on the historical archive and a contentious claim that living members of the House of Hanover were affected with the condition. A re-examination of the medical evidence and the appearance of new historical material have suggested that porphyria did indeed exist in… Expand
King George III and porphyria: a clinical re-examination of the historical evidence
TLDR
Re-examination of the evidence suggests it is unlikely that he had porphyria, and claims about peripheral neuropathy, cataracts, vocal hoarseness and abdominal pains are re-evaluated. Expand
A review of the clinical presentation, natural history and inheritance of variegate porphyria: its implausibility as the source of the ‘Royal Malady’
TLDR
It is concluded that neither George nor his relatives had porphyria, based on four principal reasons: the rarity of the disease mandates a very low prior probability, and therefore implies a vanishingly low positive predictive value for any diagnostic indicator of low specificity. Expand
Porphyria cutanea tarda: an intriguing genetic disease and marker
TLDR
The diagnosis of pseudoporphyria, which does not result from enzymatic absence, must be considered in patients with photosensitivity and cutaneous bullae, which is a serious condition in which accurate diagnosis is necessary for appropriate management. Expand
Chapter 66 – The Porphyrias
TLDR
With appropriate management, the outlook for an acute attack is good, in most cases with full recovery of neurological function, and the challenge to the neurologist is to consider the possibility of acute porphyria and obtain appropriate tests before instituting therapy with drugs, such as anticonvulsants. Expand
Henry VIII, McLeod syndrome and Jacquetta's curse.
TLDR
A critically review of the coexistence of both Kell blood group antigenicity and McLeod syndrome for Henry VIII, examining in detail the pathophysiology of these conditions and assessing the genealogy of Henry VIII and its effect in subsequent generations. Expand
The nature of King James VI/I’s medical conditions: new approaches to the diagnosis
It has been claimed that King James VI/I, an antecedent of King George III, suffered from acute porphyria, and that the disease was passed on to George III through his grand-daughter Sophie, motherExpand
Poisoning histories in the Italian renaissance: The case of Pico Della Mirandola and Angelo Poliziano.
TLDR
Heavy metals analysis showed that in Pico's remains there were potentially lethal levels of arsenic, supporting the philosopher's poisoning theory reported by documentary sources and the arsenic concentrations obtained from analysis of Poliziano's remains are probably more related to an As chronic exposure or diagenetic processes rather than poisoning. Expand
Nerve function and dysfunction in acute intermittent porphyria.
TLDR
It is proposed that porphyrin neurotoxicity causes a subclinical reduction in I(H) in AIPWN axons, whereas porphyric neuropathy may develop when reduced activity of the Na(+)/K(+) pump results in membrane depolarization. Expand
Oral arsenic treatment of leukemia and the risk of porphyria.
TLDR
PGE2 receptor subtype functionality on immature forms of human leukemic blasts and the effect of prostacyclin agonists on the differentiation of phorbol ester treated human erythroleukemia cells. Expand
Case Studies and Enrichment References
TLDR
The chapter discusses various clinical studies on disorder of fission of organelles, mitochondria, and peroxisomes, and a case study on paternal inheritance of mitochondrial DNA, which reveals an exception to the widely held concept of maternal inheritance of mitochondria DNA. Expand
...
1
2
3
4
...

References

SHOWING 1-10 OF 19 REFERENCES
Porphyria in the royal houses of Stuart, Hanover, and Prussia. A follow-up study of George 3d's illness.
TLDR
His illness had traditionally been called manic-depressive psychosis simply because it came in attacks during which he was excited, but this diagnosis did not account for the fact that he was first deranged in his severest attack at the age of 50 in 1788. Expand
Variegate porphyria and heavy metal poisoning from ingestion of "moonshine".
TLDR
In a patient with disorientation, bullous skin lesions, and a history of illicit alcohol ingestion, one must consider heavy metal intoxication and secondary porphyrin abnormalities. Expand
The "insanity" of King George 3d: a classic case of porphyria.
TLDR
The royal malady influenced the history of psychiatry, not least by dragging the " mad-business " into the limelight (Hunter and Macalpine, 1963), but only two clinical studies have been devoted to it. Expand
Porphyrins as early biomarkers for arsenic exposure in animals and humans.
TLDR
A positive correlation between the urinary arsenic levels and porphyrin concentrations demonstrated the effect of arsenic on haem biosynthesis, and significant alteration in the p Morphyrin excretion profiles of the younger age (<20 y) arsenic exposed group suggested that porphyrs could be used as early warning biomarkers for chronic exposure to arsenic. Expand
Arsenic and porphyrins.
TLDR
The increase of urinary excretion for some porphyrin homologues appears to be consistent with the inhibition by As of URO-decarboxylase in the heme biosynthesis pathway. Expand
Studies on the etiology of trace metal-induced porphyria: effects of porphyrinogenic metals on coproporphyrinogen oxidase in rat liver and kidney.
TLDR
Acute treatment studies and studies in vitro support the conclusion that the kidney is the principal source of excess urinary coproporphyrin during metal exposure, and that impairment of renal coproprophyrinogen oxidase is a principal cause of this effect. Expand
The Metabolic and Molecular Bases of Inherited Disease, 8th Edition 2001
  • C. Scriver
  • Chemistry
  • Journal of Inherited Metabolic Disease
  • 2004
I. INTRODUCTION II. PERSPECTIVES III. GENERAL THEMES IV. CANCER V. CHROMOSOMES VI. DIAGNOSTIC APPROACHES VII. CARBOHYDRATES VIII. AMINO ACIDS IX. ORGANIC ACIDS X. DISORDERS OF MITOCHONDRIAL FUNCTIONExpand
Disorders of Heme Biosynthesis
X-linked sideroblastic anemia is due to a deficiency of the erythroid form of the first enzyme in the heme biosynthetic pathway, 5-aminolevulinic acid synthase. Characteristics of the disease areExpand
Acute and chronic arsenic toxicity
TLDR
There are no evidence based treatment regimens to treat chronic arsenic poisoning but antioxidants have been advocated, though benefit is not proven, and there is increasing emphasis on using alternative supplies of water. Expand
Clinical and environmental aspects of arsenic toxicity.
TLDR
Small amounts of arsenic are metabolized in a variety of ways and are largely rapidly methylated and excreted by man and animals, and toxic manifestations in man occur at the cellular level and may appear in many organ systems. Expand
...
1
2
...