Did Mary Stuart & descendants have porphyria?

[palatine]

Does anyone know if any of the descendants of the illegitimate children of Charles II and James II suffered from porphyria?  None of James's legitimate descendants seem to have suffered from the disease, based on what I've read in their biographies.

[Tania]

Was, or is there any way of confirmation that your statement, "Psychological aspects must also have contributed, and in his final years perhaps Alzheimers as well" has been confirmed ?

Thanks for your input.

Tatiana

Yes, I agree totally.

Many of George III's royal contemporaries were descended from James (as were many of the english aristocracy). Marie Antoinette and Louis XVI were both descendants, as was the Queen of Spain, Kings of Denmark and Prussia etc. I've never understood how the porphyria gene had the forsight to follow exactly the british line of succession, when this was entirely fortuitous.

It seems to me (non-doctor) that porphyria is a condition which may be commoner in its milder forms than people may think. Perhaps the symptoms as you say overlap with other kidney (alcohol induced?) problems.

The extreme case of George III's madness can for me not be explained by porphyria alone. Psychological aspects must also have contributed, and in his final years perhaps Alzheimers as well.

[bell_the_cat]

Was, or is there any way of confirmation that your statement, "Psychological aspects must also have contributed, and in his final years perhaps Alzheimers as well" has been confirmed ?

Thanks for your input.

Tatiana

Hi Tania

I don't think even now there is a test for Alzheimers. Here's a definition from an Alzheimers site:

"Alzheimer's is a progressive, degenerative disorder that affects the brain. It damages the brain cells responsible for intellectual functioning in the brain, including memory, intelligence, judgment, and speech. Alzheimers leads to the loss of mental and physical functions.

Alzheimer's is the most common cause of dementia in older people. It affects the parts of the brain that control thought, memory, and language. A small percentage Alzheimer's patients are under 50 years of age. However, most are over 65 years of age. A rare and aggressive form of Alzheimer's can happen in some people in their 40s and 50s.

Over the course of years, as the disease progresses, individuals loose their ability to perform the basic tasks that are part of everyday life and usually end up requiring constant care and supervision. "


I don't think there's a test for "psychological causes" either, but everyone has these!

[bell_the_cat]

Does anyone know if any of the descendants of the illegitimate children of Charles II and James II suffered from porphyria?  None of James's legitimate descendants seem to have suffered from the disease, based on what I've read in their biographies.

This would include a large swathe of the English upper classes including Diana, POW and Camilla Parker-Bowles, whoops the Duchess of Cornwall.

[elena_maria_vidal]

I recently heard or read somewhere that recent examination of George III's remains reveal that he died from arsenic poisoning. Probably not a deliberate poisoning, but he may have been taking doses of arsenic over time, which people sometimes did for medicinal reasons. Has anyone heard anything about this?

[palatine]

Somehow I doubt that Camilla and other current Stuart descendants will be lining up anytime soon to be tested for porphyria.    However, I wonder if the lives of any of the eighteenth and nineteenth century descendants have been studied for symptoms of porphyria.  For example, one of Charles's descendants, the author and statesman Charles James Fox, led a very well documented life.

Elena, I saw an article in the newspaper about the possibility that George III took arsenic for various ailments, and was poisoned by it.  From what I've read about poor George's final years in biographies, he doesn't seem to have suffered from arsenic poisoning.  

[palatine]

According to Edward Corp, the heart of James II was tested for porphyria in recent years; the test results showed no sign of the disease.  Corp said that there are some questions about the provenance of the heart, and that more testing might be done on other organs of James II which were buried separately from his corpse.

There is no evidence that James II or his descendants in the legitimate line suffered from porphyria.  

[DonnaSue]

This is a very interesting site. I plan on spending time doing a lot of reading here as participants seem to have a lot of interesting information that one could learn from.

I'm new here and stumbled upon this site when searching for info on porphyria. I am maternally descended from old European aristocracy/royalty and when reading about an ancestor I stumbled upon the mention of porphyria. Looking into it further I discovered that it just might be the explanation for some of the mysterious problems that seem to run in our family that doctors can't quite put a finger on. Myself, my youngest daughter and one of my nieces have an 'allergy' to the sun where we develop an itchy rash and sometimes little blisters usually in the beginning of the sunny season. After we get a bit of a tan the symptoms seem to fade. A good portion of my family are photosensitive and wear dark glasses year round out of doors, even on 'bright' cloudy days. My little one becomes extremely light sensitive when she has a cold/is sick and will literally cry and run to hide in a dark room as just normal lighting is blinding and painful to her eyes. Many of us have a history of unexplained stomach pains, and all that goes with that topic. My sister and my niece have been told they have fibromyalgia, yet drugs of any type rarely do much to alleviate their discomfort. We all get the unexplained tingling and numbness in our extremities, tho no one has ever become paralyzed by these symptoms. My sister and I both get the racing heart symptoms from time to time, yet the doctors say we have no heart problems that they can find.
I'm encouraging my sister and niece to be tested as they seem to suffer from the symptoms the most and to a higher degree and are more likely better test subjects than others of us within the family.
If anyone has ever come across any further information regarding this disease please post it, any info would be appreciated.

[DonnaSue]

Attention DNAGenie:

Hi B......,

I would be happy to chat with you about this subject. Please message me with an email addy to use as I've not had good luck with using the internal messaging system on this board.
I tried to reply to your message and wasn't able to get it to go through. I look forward to hearing from you.

Regards,
Donna-Sue

[DNAgenie]

Earlier posters asked about porphyria symptoms so I thought it might be useful to outline the symptoms of Acute Intermittent Porpyhria, as described in Purple Secret.  AIP is the most common form of the disease and one of the main candidates for the malady in the Royal Stuarts.

From Purple Secret (1998) by John C.G. Rohl, Martin Warren and David Hunt. p 244-245:

Acute Intermittent Porphyria (AIP) is the most common of the inherited porphyrias and is caused by a deficiency in the enzyme porphobilinogen deaminase (PBGD). A deficiency in this enzyme leads to the accumulation of the early pathway intermediates porphilobinogen (PBG) and ALA, which are excreted in the urine of patients during an attack. The excretion of PBG can give rise to the presence of coloured urine, usually red or brown.  More often, the colour of urine develops with time after it is left to stand.  AIP is normally triggered by factors such as diet, hormones and drugs. The disorder is generally expressed after puberty and with a higher incidence in women than in men, perhaps reflecting the greater fluctuation in hormone levels.

There have been a number of clinical studies on the incidence of the symptoms of AIP.  In all cases, around 90 per cent of patients suffer from abdominal pain, with a majority also suffering from vomiting and constipation.  Patients were also found to suffer from limb, head, neck or chest pains, muscle weakness, hypertension and tachycardia and to display mental symptoms. In addition, some patients reported convulsions, sensory loss, breathing difficulties and fever.  The abdominal pains are often severe enough to warrant surgical exploration.  If this is accompanied by a barbiturate-based anaesthetic, it often makes the AIP more acute and can lead to death. In severe cases, the urine of the patient has a port-wine colour due to the concentration of excreted PBG and its chemical derivatives.

Patients can become hypersensitive, anxious, restless, insomniac, paranoic or depressed and, in some cases, have been labelled as hysterical. The high incidence of AIP patients in psychiatric institutions shows how easy it is to misdiagnose the disorder.  All of the major symptoms of AIP are thought to be caused by the effect of the early pathway intermediates on the nervous system, causing it to function incorrectly.  However the exact cause and site of the dysfunctions are still unknown.  AIP is thought to occur in about one in ten thousand of the population, although the actual frequency may be even higher than this.

One of the problems in assessing the level of occurrence of AIP is that about 90 per cent of people who carry the defective gene for AIP never display any symptoms.  The reasons why so many carriers remain asymptomatic is unclear.  One point which is certain is that AIP can be induced in carriers by a number of factors, including certain drugs, alcohol and hormones.  The main effect of these factors is to increase the level of activity of the enzyme which makes ALA, the starting point of haem biosynthesis.  The increased concentration of ALA leads to an increase of flow of intermediates through the haem pathway, an increase which most healthy individuals can cope with.  However, AIP patients have a reduced level of PBGD and thus the pathway in these individuals cannot cope with the increase in rate and a bottleneck forms at this point.  An increase in ALA and PBG occurs and these elevated levels consequently lead to the neurophysiological problems associated with an AIP attack. Progesterone and oestrogen, endocrine hormones associated with women’s menstrual cycles, are also known to influence AIP attacks.  On the whole, AIP is rarely manifested before puberty and there is a drop in the level of AIP attacks in post-menopausal women.  Overall, AIP is more common in women than men (at a ratio of three women to two men suffer with AIP) and women are more susceptible to AIP attacks at the start of their period.  A number of women AIP sufferers have reported a periodicity of attacks which reflects their menstrual cycle.  Certain contraceptive pills also cause attacks in women carriers of the disorder.

Poor diet is also a major influence on AIP attacks. In general it is thought that a low caloric diet can increase the likelihood of an attack, and, consequently, AIP sufferers are more likely to precipitate an attack if they go on a crash diet.

[DNAgenie]

Another form of porphyria, and the type favoured by the authors of Purple Secret as most likely to be the cause of disease in the Stuarts and the Hohenzollerns, is Variegate Porphyria. From Purple Secret, pp 245-247:

Variegate porphyria arises from a dysfunction in the enzyme protoporphyrinogen oxidase (PPOX), the penultimate enzyme of the haem biosynthesis pathway. As the name implies, variegate porphyria is a mixed porphyria in which sufferers display symptoms of acute (neurovisceral) porphyria and/or photosensitivity.  The photosensitivity is due to the accumulation of protoporphyrin.

Variegate porphyria occurs with a much higher incidence in South Africa than the rest of the world. As explained in Chapter 1, this was a result of the marriage between two Dutch settlers at the Cape of Good Hope in 1688. The relative isolation of the community where they settled allowed for a rapid propagation of the mutant gene for variegate porphyria. Biochemical studies have shown that carriers of the mutant variegate porphyria gene have a 50 per cent reduction in PPOX. More recently, with the isolation of the gene, it has been possible to determine the actual mutation which caused the South African porphyric malady.  PPOX contains 477 amino acids and the mutation within the gene changes just one of those amino acids (the amino acid at position 59 is changed from an arginine to a tryptophan). Through this seemingly innocuous change of just one amino acid, the enzyme is rendered completely inactive. However, as predicted nearly thirty years ago, variegate porphyria sufferers in Europe do not have the same mutation, thus explaining why sufferers in Europe do not exhibit exactly the same symptoms as those in South Africa.  Overall variegate porphyria should be considered a world-wide problem occurring with only a slightly lower incidence than AIP.

In terms of symptoms, variegate porphyria is very similar to AIP except that photosensitivity is much more common.  Thus patients describe a very similar range of neurovisceral symptoms to those observed in acute porphyria, including acute abdominal pain, peripheral muscular weakness and psychiatric symptoms.  The photosensitivity results in the appearance of vesicles and bullae, increased skin pigmentation, hair growth and skin fragility.  The skin fragility means that if the skin is pushed under pressure it appears to slide.  As one might expect, photosensitivity is more marked in countries where there is a good deal of sunshine. 

The major biochemical finding associated with variegate porphyria is the excretion of large amounts of protoporphyrin in the faeces.  Faeces of variegate porphyria sufferers appear fluorescent when viewed under ultraviolet light, and this was a basic diagnostic test for variegate porphyria in the early days.  The same factors which influence AIP attacks also influence variegate porphyria.  Thus barbiturates, contraceptive steroids and dietary changes all have an effect on either starting or exacerbating variegate porphyria attacks.

[Mariel]

I am a newbie here, so there is a lot I do not know, but on the subject of porphyira, I know some things, as I have it.  I
believe mine may have come down the centuries from the middle ages, when my family of that time which settled in Scotland
were close followers of the Stuarts.  By followers I mean literally followers who came with the Stuarts from France to England
and finally to Scotland, where they settled in the region now called Pollock Park in Glasgow (along with Walter FitzAllen, the
first "Stuart" to live full time in Scotland.

The question has arisen here as to whether anyone prior to James V of Scotland had porphyria, on this line.  Yes, probably
the Tudors had it, the forebears of Mary Queen of Scots and Lord Darnley.  Sometimes people "pass on" Porphyria with
minimal symptoms, although the disease is not "recessive."  (it is "dominant", so that an average of 50% of children get it).
I believe the outstanding candidate for Porphyria on the Tudor line was Charles VI of France, who was considerably madder
than George III, and was parent of Katherine of Valois, who married Owen Tudor as her second husband.  Porphyria madness,
as has been stated here, usually is not constant.  It happens when the metabolic pathways which are damaged are triggered,
by foods, chemicals, medicines, infections, and stress.  So most "porphs" are not crazy all of the time, and some of us are
never crazy at all, although almost all of us have depressions and difficulty focusing when in "attack". 

I believe the family which became the Stuarts (elected by the elites of Scotland from the landowning class) had porphyria
much earlier than is usually discussed, but of course that is speculation.  They were influenced by other porphyria lines
entering their genetic structure, most notably the Hungarians who came to Scotland with Queen Margaret, even before the
Stuarts settled in Scotland.  There are MANY porphyria lines and Scotland was a melting pot of peoples, both in the landowning
classes and later the nobility,and in the common people. So porphyria lines probably came from many places, and then were
exacerbated by inbreeding, especially among the landowners and nobility.  Some of the related families would never let a good
cousin marriage go to waste, to preserve fortunes and lands. 

Porphyria is a neuro-visceral disease and metabolic disease which causes poisoning of nerves.