The Madness of King George and the Royal Malady: Porphyria
It sounds like the stuff of fiction: a rare genetic defect in a royal family's bloodline that can cause debilitating illness, madness, and death. Except that in the case of England's royal family, the disorder is real, and its devastating effects can be traced through Mary, Queen of Scots and James II to George III and Alexei Romanov, the last Tsarevich of Russia. The disorder is called Porphyria.
Porphyria is caused by a defect in the gene governing one of a series of enzymes that converts substances in the body known as porphyrins into heme (heme, of course, is a necessary component of hemoglobin and other important hemoproteins). There are more than half a dozen different types of porphyria, depending on which enzyme in the biosynthetic pathway is affected. George III suffered from Variegate Porphyria, caused by a genetic defect in the final enzyme in the chain.
People with Porphyria can suffer a life-long series of "attacks" that occur when a drop in the production of the effected enzyme leads to a drop in the production of heme. The body, sensing the need for more hemoglobin, signals the liver to produce more porphyrins. But since the body isn't converting porphyrins to heme, the porphyrins—which are toxic in excess numbers—build up in the system and cause an attack. The body basically suffers from a double whammy: a toxic build up of porphyrins combined with a lack of sufficient hemoglobin and heme.
A minor attack can involve heart palpitations, a feeling of general unwellness, and—depending upon the variety of porphyria—an allergic reaction to the sun. An acute attack feels more like a sudden onset of the worst kind of flu, with weakness, severe abdominal distress, fever and chills, and mental confusion. If the attack is particularly acute or left untreated, it can lead to numbness and then paralysis of the limbs, hallucinations, peripheral neuropathy, brain damage, coma, and death.
An attack can be triggered by a variety of factors, including chemical exposure, modern pharmaceuticals, stress, viral infections, hormonal fluctuations (especially pregnancy or a woman's monthly cycle), alcohol, and a low carbohydrate diet or fasting. Because an attack can feel so much like a severe case of the flu or food poisoning, even those who know they suffer from porphyria are sometimes slow to recognize an attack for what it is.
Porphyria was once thought to be an extremely rare disorder in the United States. As a result, medical personnel in this country are dangerously unfamiliar with this syndrome. Mention porphyria to most doctors and they'll usually wrinkle their foreheads and say, "What's that?" or perhaps, "Um...that has something to do with dark urine, doesn't it?" (Those suffering from a porphyria attack can sometimes display a darkened urine as the body attempts to throw off the excess porphyrins, but this is not always the case.) Most pophyrias are inherited, although there is one type that can be acquired due to chemical exposure. There is increasing evidence that many of those suffering from exposure to Agent Orange and from Gulf War Syndrome actually have this acquired form of porphyria. As a result, more studies are now being done on what was until recently considered an extremely rare problem.
But ignorance on the part of medical personnel is still common, and can be extremely dangerous, since modern medical procedures often provoke an attack. Many drugs—from barbiturates to the traces of mercury in vaccines—can cause an attack. Some now believe porphyria may be the link between vaccines and autism. Many of those who die during or after surgery due to reactions to anesthetics are undiagnosed porphyriacs, as are many of those who die from chemotherapy. Hospital personnel will rarely recognize a porphyria patient brought into the emergency room. Yet standard treatment for a patient with acute abdominal distress—an anti-nausea drip—can kill a porphyria sufferer.
Unfortunately, porphyria is an extremely difficult disorder to detect. The common tests for the disorder—a blood, urine, or stool test—are only effective immediately after an attack. Furthermore, most labs are unfamiliar with the tests and frequently perform them wrong, although many doctors are unaware of this. DNA testing is now possible, and reliable, but expensive.
Those who carry porphyria can go for years without suffering an attack, for the disorder does not usually manifest until puberty or even later. Women seem to be more susceptible to attacks than men, both because of women's lower tolerance for a high protein diet and because of their fluctuating hormone levels. Women who are in their cycle, taking birth control pills, or pregnant, are most susceptible to an attack. Popular diets such as South Beach, Atkins, and Scarsdale have also provoked many acute attacks, since porphyriacs must maintain a high carb intake. Porphyriacs should never, ever fast.
Generally, porphyriacs are advised to maintain as natural and healthy a lifestyle and environment as possible. Because the liver is already severely taxed by the continuous need to remove excess porphyrins from the system (even in those who have never actually suffered an acute attack), anything else that taxes the liver should be avoided. This includes most drugs (over the counter and prescription), alcohol, excess protein consumption, and exposure to heavy metals and chemicals. Porphyriacs should avoid exposure to pesticides, both in the home and as a residue on food. Additives such as artificial sweeteners, MSG, and various dyes and flavorings should also be avoided, and natural cleaning products preferred whenever possible.
The treatment for a mild attack can be surprisingly simple, if it is recognized in time, and depending on the cause. For someone whose attack is brought on by low carb consumption, the immediate consumption of something as simple as a bottle of apple juice and a few cookies will often be enough to pull a porhyriac out of an attack, particularly if she is young and otherwise healthy. But because it seems counterintuitive—giving cookies to someone who's vomiting!—this simple remedy is often overlooked. More serious attacks can require heme and a glucose drip, and take months to recover from. Some porhyriacs suffer chronic attacks to the point they are in constant pain and require morphine. Even porphyriacs who know about and manage their condition still die from it.
Because porphyria can affect electrolyte balances and the body's ability to absorb vitamin K (for reasons not yet understood), some variegate porphyria sufferers have extreme trouble with their blood not clotting. There are those who have suggested that the last tzarevich of Russia, Alexei, son of Nicholas and Alexandria, may actually have suffered from porphyria rather than hemophilia. Various aspects of his case are suggestive of porphyria rather than hemophilia, including the ability of the monk Rasputin to aid the boy by calming him. Porphyria attacks can be provoked or worsened by stress.
As for England's George III, the King's doctors treated his attacks by dosing him with massive amounts of mercury and arsenic, and by bleeding him, all of which actually cause attacks themselves. It's a tribute to the man's constitution that they didn't kill him, although he obviously suffered permanent brain damage.
Interestingly, there is evidence that both the Prince Regent and his wife, the Princess Caroline, also suffered from porphyria. Caroline was, after all, the Regent's first cousin. Their daughter, Princess Charlotte, also seems to have had the disorder, which likely contributed to her death in childbirth.
Various members of the Royal House of Stuart, including James II, also manifested symptoms of porphyria. The personality changes James II exhibited in later life (such as his development of extreme anxiety) were probably caused by his porphyria. The disorder also manifested in Queen Victoria, and in various members of Queen Elizabeth II's family, including her sister, Margaret—although only a cousin, Prince William of Gloucester, has actually admitted to having porphyria. The royal houses of Stuart and Hanover are both believed to have inherited their porphyria from the same source: Mary, Queen of Scots. Beyond that, the origins of the genetic disorder are lost in the mists of time.
If you suspect you or someone you love may have porphyria, you can learn more about the disorder from the American Porphyria Foundation, or from Porphyria South Africa. For more about porphyria and the royal families of Europe, see Purple Secret: Genes, 'Madness' and the Royal Houses of Europe, by John Rohl, Martin Warren, and David Hunt.
It sounds like the stuff of fiction: a rare genetic defect in a royal family's bloodline that can cause debilitating illness, madness, and death. Except that in the case of England's royal family, the disorder is real, and its devastating effects can be traced through Mary, Queen of Scots and James II to George III and Alexei Romanov, the last Tsarevich of Russia. The disorder is called Porphyria.
Porphyria is caused by a defect in the gene governing one of a series of enzymes that converts substances in the body known as porphyrins into heme (heme, of course, is a necessary component of hemoglobin and other important hemoproteins). There are more than half a dozen different types of porphyria, depending on which enzyme in the biosynthetic pathway is affected. George III suffered from Variegate Porphyria, caused by a genetic defect in the final enzyme in the chain.
People with Porphyria can suffer a life-long series of "attacks" that occur when a drop in the production of the effected enzyme leads to a drop in the production of heme. The body, sensing the need for more hemoglobin, signals the liver to produce more porphyrins. But since the body isn't converting porphyrins to heme, the porphyrins—which are toxic in excess numbers—build up in the system and cause an attack. The body basically suffers from a double whammy: a toxic build up of porphyrins combined with a lack of sufficient hemoglobin and heme.
A minor attack can involve heart palpitations, a feeling of general unwellness, and—depending upon the variety of porphyria—an allergic reaction to the sun. An acute attack feels more like a sudden onset of the worst kind of flu, with weakness, severe abdominal distress, fever and chills, and mental confusion. If the attack is particularly acute or left untreated, it can lead to numbness and then paralysis of the limbs, hallucinations, peripheral neuropathy, brain damage, coma, and death.
An attack can be triggered by a variety of factors, including chemical exposure, modern pharmaceuticals, stress, viral infections, hormonal fluctuations (especially pregnancy or a woman's monthly cycle), alcohol, and a low carbohydrate diet or fasting. Because an attack can feel so much like a severe case of the flu or food poisoning, even those who know they suffer from porphyria are sometimes slow to recognize an attack for what it is.
Porphyria was once thought to be an extremely rare disorder in the United States. As a result, medical personnel in this country are dangerously unfamiliar with this syndrome. Mention porphyria to most doctors and they'll usually wrinkle their foreheads and say, "What's that?" or perhaps, "Um...that has something to do with dark urine, doesn't it?" (Those suffering from a porphyria attack can sometimes display a darkened urine as the body attempts to throw off the excess porphyrins, but this is not always the case.) Most pophyrias are inherited, although there is one type that can be acquired due to chemical exposure. There is increasing evidence that many of those suffering from exposure to Agent Orange and from Gulf War Syndrome actually have this acquired form of porphyria. As a result, more studies are now being done on what was until recently considered an extremely rare problem.
But ignorance on the part of medical personnel is still common, and can be extremely dangerous, since modern medical procedures often provoke an attack. Many drugs—from barbiturates to the traces of mercury in vaccines—can cause an attack. Some now believe porphyria may be the link between vaccines and autism. Many of those who die during or after surgery due to reactions to anesthetics are undiagnosed porphyriacs, as are many of those who die from chemotherapy. Hospital personnel will rarely recognize a porphyria patient brought into the emergency room. Yet standard treatment for a patient with acute abdominal distress—an anti-nausea drip—can kill a porphyria sufferer.
Unfortunately, porphyria is an extremely difficult disorder to detect. The common tests for the disorder—a blood, urine, or stool test—are only effective immediately after an attack. Furthermore, most labs are unfamiliar with the tests and frequently perform them wrong, although many doctors are unaware of this. DNA testing is now possible, and reliable, but expensive.
Those who carry porphyria can go for years without suffering an attack, for the disorder does not usually manifest until puberty or even later. Women seem to be more susceptible to attacks than men, both because of women's lower tolerance for a high protein diet and because of their fluctuating hormone levels. Women who are in their cycle, taking birth control pills, or pregnant, are most susceptible to an attack. Popular diets such as South Beach, Atkins, and Scarsdale have also provoked many acute attacks, since porphyriacs must maintain a high carb intake. Porphyriacs should never, ever fast.
Generally, porphyriacs are advised to maintain as natural and healthy a lifestyle and environment as possible. Because the liver is already severely taxed by the continuous need to remove excess porphyrins from the system (even in those who have never actually suffered an acute attack), anything else that taxes the liver should be avoided. This includes most drugs (over the counter and prescription), alcohol, excess protein consumption, and exposure to heavy metals and chemicals. Porphyriacs should avoid exposure to pesticides, both in the home and as a residue on food. Additives such as artificial sweeteners, MSG, and various dyes and flavorings should also be avoided, and natural cleaning products preferred whenever possible.
The treatment for a mild attack can be surprisingly simple, if it is recognized in time, and depending on the cause. For someone whose attack is brought on by low carb consumption, the immediate consumption of something as simple as a bottle of apple juice and a few cookies will often be enough to pull a porhyriac out of an attack, particularly if she is young and otherwise healthy. But because it seems counterintuitive—giving cookies to someone who's vomiting!—this simple remedy is often overlooked. More serious attacks can require heme and a glucose drip, and take months to recover from. Some porhyriacs suffer chronic attacks to the point they are in constant pain and require morphine. Even porphyriacs who know about and manage their condition still die from it.
Because porphyria can affect electrolyte balances and the body's ability to absorb vitamin K (for reasons not yet understood), some variegate porphyria sufferers have extreme trouble with their blood not clotting. There are those who have suggested that the last tzarevich of Russia, Alexei, son of Nicholas and Alexandria, may actually have suffered from porphyria rather than hemophilia. Various aspects of his case are suggestive of porphyria rather than hemophilia, including the ability of the monk Rasputin to aid the boy by calming him. Porphyria attacks can be provoked or worsened by stress.
As for England's George III, the King's doctors treated his attacks by dosing him with massive amounts of mercury and arsenic, and by bleeding him, all of which actually cause attacks themselves. It's a tribute to the man's constitution that they didn't kill him, although he obviously suffered permanent brain damage.
Interestingly, there is evidence that both the Prince Regent and his wife, the Princess Caroline, also suffered from porphyria. Caroline was, after all, the Regent's first cousin. Their daughter, Princess Charlotte, also seems to have had the disorder, which likely contributed to her death in childbirth.
Various members of the Royal House of Stuart, including James II, also manifested symptoms of porphyria. The personality changes James II exhibited in later life (such as his development of extreme anxiety) were probably caused by his porphyria. The disorder also manifested in Queen Victoria, and in various members of Queen Elizabeth II's family, including her sister, Margaret—although only a cousin, Prince William of Gloucester, has actually admitted to having porphyria. The royal houses of Stuart and Hanover are both believed to have inherited their porphyria from the same source: Mary, Queen of Scots. Beyond that, the origins of the genetic disorder are lost in the mists of time.
If you suspect you or someone you love may have porphyria, you can learn more about the disorder from the American Porphyria Foundation, or from Porphyria South Africa. For more about porphyria and the royal families of Europe, see Purple Secret: Genes, 'Madness' and the Royal Houses of Europe, by John Rohl, Martin Warren, and David Hunt.