Despite lacking the modern molecular techniques accessible today, he came to accurate conclusions that describe haemochromatosis disease as an inborn error of metabolism where this inherited disorder can increase the absorption of iron and thus cause tissue damage due to iron deposition. Moreover, he rejected theories that alcohol, drug, and other factors contribute to the disorder.The clinical case series from 1935 to 1955 indicated that haemochromatosis was more common than had been acknowledged. During the 1960s, MacDonald, a pathologist at Boston City Hospital, diverted attention away from the true cause of haemochromatosis. He believed that haemochromatosis was a nutritional condition because he observed many drunken patients of Irish ancestry. During this period of time, other investigators reported additional evidence suggesting that a genetic factor could play a central role in the absorption of iron in people with haemochromatosis. However, alcohol consumption is known to increase the risk of liver injury in haemochromatosis. This finding is consistent with the concept that excess iron metabolism is a primary cause of haemochromatosis disease.Finally, in 1976, Marcel Simon and his collaborators confirmed that haemochromatosis is an autosomal recessive disorder that has a link to the human leukocyte antigen (HLA) region of the genome. It took 20 years for researchers at Mercator Genetics to effectively identify and clone the haemochromatosis genes using a positional cloning approach.In 1996, Feder et al. identified HFE, which is a major histocompatibility complex (MHC) gene. They found that 83% of patients have homozygosity for a missense mutation (C282Y) in the HFE gene.
In 2005, it was suggested that arsenic (which is known to be porphyrogenic) given to George III with antimony may have caused his porphyria. This study found high levels of arsenic in King Georges 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. 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 Kings symptoms suggest that he had porphyria and notes 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 in his new biography, "The Last King of America." 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 (Emperor William IIs eldest sister) and her daughter Princess Feodora of Saxe-Meiningen. They uncovered better evidence that George IIIs great-great-great-grandson Prince William of Gloucester was reliably diagnosed with variegate porphyria. Mary, Queen of Scots. It is believed that Mary, Queen of Scots, King George IIIs ancestor, also had acute intermittent porphyria, although this is subject to much debate.