King George II and Porphyria

Some historians blame the American Revolution on a blood disease--an abnormality of hemoglobin that afflicted King George III, who ruled England at the time. So puzzling were his symptoms that not until this century did medical researchers discover the underlying disorder, called porphyria.

At age 50, the king first experienced abdominal pain and constipation, followed by weak limbs, fever, a fast pulse, hoarseness, and dark red urine. Next nervous system symptoms began, including insomnia, headaches, visual problems, restlessness, delirium, convulsions, and stupor. His confused and racing thoughts, combined with his ripping off his wig and running about naked while at the peak of a fever, convinced court observers that the king was mad. Just as Parliament was debating his ability to rule, he mysteriously recovered.

But George's plight was far from over. He suffered a relapse 13 years later, then again 3 years after that. Always the symptoms appeared in the same order, beginning with abdominal pain, fever, and weakness and progressing to the nervous system symptoms. Finally, an attack in 1811 placed him in an apparently permanent stupor, and he was dethroned by the Prince of Wales. He lived for several more years, experiencing further episodes of his odd affliction.

In George III's time, doctors were permitted to do very little to the royal body and based their diagnoses on what the king told them. Twentieth-century researchers found that George's red urine was caused by an inborn error of metabolism. In porphyria, because of the absence of an enzyme, part of the blood pigment hemoglobin, called a porphyrin ring, is routed into the urine instead of being broken down and metabolized by cells. Porphyrin builds up and attacks the nervous system, causing many of the other symptoms. Examination of physicians' reports on George's relatives--easy to obtain for a royal family--showed that several of them had symptoms of porphyria as well. The underlying defect in red blood cell recycling had appeared in its various guises as different problems.

Back to Readings