Did Mary Stuart & descendants have porphyria?

Thanks for that Helen.   As I said, I doubted she had porphyria.   Goodness knows she was plagued, especially in her latter years, with major, non-porphyria associated illness.

tsaria

Now I recall, I have read somewhere (don't ask me where) that Pcss Margaret was asked outright whether she did indeed suffer from porphyria and that she replied in the negative; she did however add that she knew that William of Gloucester suffered from it.
And Tsaria you are right, illness of every kind was always close in her later years.  A great shame as she had been a woman of style (and temperament it must be added); her decline was very sad to see and a marked contrast to the robust health of her sister...

Does anyone know exactly how porphyria is inherited?

Does anyone know exactly how porphyria is inherited?

Porphyria is not always inherited. Exposure to toxic substances can cause symptomatic porphyria, as will contracting Hepatitis C, excessive drug and alcohol use. However the majority of cases are due to inheritance.

Depending on the type of porphyria, it may be due to an autosomal dominant trait (where only one copy of the gene is required) or it may be due to an autosomal recessive trait (where both parents must contribute the defective enzymic gene).

Furthermore presence of the defective gene does not necessarily mean that the condition will become symptomatic.

Thanks, Belochka!  I don't know if I am interpreting this correctly, but if this is a dominant genetic trait, shouldn't we see a lot more manifestation of this disease in the Stuarts and descendants (if passed down by Mary Stuart or one of her own ancestors)? Or are they mostly asymptomatic?

 I don't know if I am interpreting this correctly, but if this is a dominant genetic trait, shouldn't we see a lot more manifestation of this disease?  

Don't forget that the offspring have a 50% probability of inheriting the defective gene, where one parent posseses the porphyria gene.

Also depending on the type of enzyme which is affected in the metabolic pathway in the biosynthesis of the heme molecule, will predict which porphyria symptoms will manifest. These symptoms can mimic some other condition, without considering porphyria as being the cause. Without confirmatory diagnostic testing, then one cannot be certain that porphyria was or was not the problem.

Furthermore, in some cases specific triggers maybe required  for the condition to present, such as sunlight or ingestion of certain food. By this example, if those triggers have not been activated, then the person will remain asymptomatic for life.

As you can see there are many ifs ....  

Probably many of them did manifest it, but were not diagnosed. And maybe the connection among them wasn't made because the symptoms can be so varied...

Exactly Helen!

A full medical history will remain incomplete.

Belochka may well be able to advise.   Could another answer to Mary's acute abdominal pains be answered with the simple explanation of mittelschmerz?  

Although the reports of Mary, Queen of Scots abdominal pains appear to be at the extreme end of the spectrum, this is a possiblity which I am not aware has been addressed.

tsaria

Good possibility, Tsaria. I've had that one myself.  

Belochka may well be able to advise.   Could another answer to Mary's acute abdominal pains be answered with the simple explanation of mittelschmerz?  
tsaria

Hi Tsaria,

Could you please advise me of all other symptoms which Mary was said to have experienced. I know nothing about this lady. How old was she during these episodes? What was the frequency of her distress?

Abdominal pain is too broad a description to make any probable clinical diagnosis.

One cannot exclude perimenstrual distress (lower abdominal pain before or during menses) or perhaps endometriosis?? There are many options to select from.

In "The Sickly Stuarts: The Medical Downfall of a Dynasty" by Dr. Frederick Holmes, the medical case histories of the six Stuart sovereigns are examined in detail.  Holmes rejects the idea that King James had porphyria, since he believes that the main symptom that manifested in James was discolored urine, "red as Alicante wine."  Holmes does not believe that the environmental factors that usually cause porphyria or trigger it in those with a propensity for it were present in James's environment.

Holmes details the severe problems King James had with his kidneys.  One of them was tiny and probably dysfunctional, a congenital birth defect.  The other was riddled with kidney stones, which Holmes believes caused blood to mix with his urine, leading to the discoloration.  

Holmes does not devote more than a brief mention to James's daughter Elizabeth, who does not seem to have suffered from kidney disease or kidney stones.  However, biographies of Elizabeth and her family reveal that two of Elizabeth's sons, Rupert and Gustav, suffered from kidney stones.

Elizabeth's daughter Sophia was the mother of George I.  There is no evidence that Sophia suffered from kidney problems.  However, if two of her brothers suffered from them, as well as her grandfather, it seems possible that she could have passed the problem on to her descendants.

I have only recently begun reading McAlpine's book "George III and the Mad-Business", and I have yet to acquire a copy of Rohl's book, but it is my understanding that they studied only Sophia's descendants.  Two of Sophia's brothers, Edward and Karl-Ludwig, left daughters whose descendants married into almost every Catholic royal family in Europe.   The House of Habsburg can trace their line to Karl-Ludwig through the marriage of his great-grandson, Francis of Lorraine, to Empress Maria Theresa of Austria.

If porphyria was truly a common and hereditary problem inherited from Mary Queen of Scots, then Catholic and Protestant descendants alike would be sufferers.  I hope a future study will be done that includes a random sampling of the descendants of Sophia's brothers.

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.

Excuse my "gormlessness" but re Palatine's post; how do we know James had a tiny probably dysfunctional kidney. Did they do  post mortem on him  

King James had an autopsy which revealed his kidney problems.

Elizabeth did not have an autopsy.  She had thirteen children, but only two had autopsies, Gustav and Rupert.  Neither was diagnosed with kidney stones or kidney problems in their lifetimes.

I just bought a book called 'The Sickly Stuarts' about the Medical history of the Stuarts. Since I am already reading two other books, I won't be looking at it for a while, but when I do, I'll post any interesting info!