Computer-based diagnosis of illness in historical persons.

Retrospective diagnosis of illness in historical figures is a popular but somewhat unreliable pastime due to the lack of detailed information and reliable reports about clinical features and disease progression. Modern computer-based diagnostic programmes have been used to supplement historical documents and accounts, offering new and more objective approaches to the retrospective investigations of the medical conditions of historical persons. In the case of King George III, modern technology has been used to strengthen the findings of previous reports rejecting the popular diagnosis of variegate porphyria in the King, his grandson Augustus d'Esté and his antecedent King James VI and I. Alternative diagnoses based on these programmes are indicated. The Operational Criteria in Studies of Psychotic Illness (OPCRIT) programme and the Young mania scale have been applied to the features described for George III and suggest a diagnosis of bipolar disorder. The neuro-diagnostic programme SimulConsult was applied to Augustus d'Esté and suggests a diagnosis of neuromyelitis optica rather than acute porphyria with secondarily multiple sclerosis, as proposed by others. James VI and I's complex medical history and the clinical features of his behavioural traits were also subjected to SimulConsult analysis; acute porphyria was rejected and the unexpected diagnosis of attenuated (mild) Lesch-Nyhan disease offered. A brief review of these approaches along with full reference listings to the methodology including validation are provided. Textual analysis of the written and verbal outputs of historical figures indicate possible future developments in the diagnosis of medical disorders in historical figures.

Variegate porphyria in South Africa, 1688-1996--new developments in an old disease.

Variegate porphyria, an autosomal dominant inherited trait resulting in decreased activity of protoporphyrinogen oxidase, the penultimate haem biosynthetic enzyme, is characterised clinically by photosensitive skin disease and a propensity to acute neurovisceral crises. The disease has an exceptionally high frequency in South Africa, owing to a founder effect. The specific mutation in the protoporphyrinogen oxidase gene sequence which represents this founder gene has been identified. Genetic diagnosis is therefore now possible in families in whom the gene defect is known. However, the exact nature and degree of activity of the porphyria can only be determined by detailed quantitative biochemical analysis of excreted porphyrins. The relative contributions of the acute attack and the skin disease to the total disease burden of patients with variegate porphyria is not static, and in South Africa there have been significant changes over the past 25 years, with fewer patients presenting with acute attacks, leaving a greater proportion to present with skin disease or to remain asymptomatic with the diagnosis being made in the laboratory. The most common precipitating cause of the acute attack of VP is administration of porphyrinogenic drugs. Specific suppression of haem synthesis with intravenous haem arginate is the most useful treatment of a moderate or severe acute attack. Although cutaneous lesions are limited to the sun-exposed areas, management of the skin disease of VP remains inadequate.