The princess was pregnant with a child which was expected to be the heir in the next generation to the British throne. In some cases the jam is total, preventing any heme synthesis at all. In: Neurology in Clinical Practice, 6th Edition. [5], Acute intermittent porphyria (AIP), variegate porphyria (VP), aminolevulinic acid dehydratase deficiency porphyria (ALAD) and hereditary coproporphyria (HCP). [50] The worldwide prevalence has been estimated to be between one in 500 and one in 50,000 people. [41] Magnesium sulfate and bromides have also been used in porphyria seizures; however, development of status epilepticus in porphyria may not respond to magnesium alone. There are several different types of porphyria that are known and all vary in severity. People who have inherited porphyria from one or both parents have deficiencies in certain enzymes that help with normal hemoglobin functions. A high-carbohydrate diet is typically recommended; in severe attacks, a dextrose 10% infusion is commenced, which may aid in recovery by suppressing heme synthesis, which in turn reduces the rate of porphyrin accumulation. [4], The most severe episodes may involve neurological complications: typically motor neuropathy (severe dysfunction of the peripheral nerves that innervate muscle), which leads to muscle weakness and potentially to quadriplegia (paralysis of all four limbs) and central nervous system symptoms such as seizures and coma. Although the prevalence of this disease is considered rare, there is a direct connection to the diagnosis of Porphyria Cutanea Tarda and a persons exposure to Agent Orange. More than 200 genetic variants of AIP are known, some of which are specific to families, although some strains have proven to be repeated mutations. Both Plutarch and Suetonius suggest that Caesars symptoms were caused by epilepsy, a chronic neurological disorder that was well known to the ancients. The signs may present from birth and include severe photosensitivity, brown teeth that fluoresce in ultraviolet light due to deposition of Type 1 porphyrins, and later hypertrichosis. www scuola test verifica sulle regioni del nord italia. "Sometimes the road less traveled is less traveled for a reason." Jerry Seinfeld (February 1997) 4. [1] The underlying mechanism results in a decrease in the amount of heme produced and a build-up of substances involved in making heme. There are seven different types of porphyria and in most cases, they are inherited. [2] They may be inherited in an autosomal dominant, autosomal recessive, or X-linked dominant manner. Mass General Porphyria Center. In others, it is only partial, permitting limited heme synthesis. It could be a decision that makes life a whole lot easier. [16] All samples to detect porphyrins must be handled properly. 1. Kurt Cobain. List of Famous People with Paraplegia, loosely ranked by fame and popularity. The pain, burning, swelling, and itching that occur in erythropoietic porphyrias generally require avoidance of bright sunlight. At its worst, CEP causes appalling photomutilations from the light-activated porphyrins, including loss of facial features and fingers, scarring of the cornea and blindness. Previous 3 answers Next The king Georges III, the lady with the tattoos Posted Mar 30, 2019 by Marie 2500 The King Georges the third Posted May 10, 2020 by Deemay 100 Sean Albright - American racecar driver has Variegate Porphyria (VP) George III. Porphyrias usually develop because of an inherited genetic mutation. Finally, and most important, the fact that vampire reports were literally rampant in the 18th century, and that congenital erythropoietic porphyria is an extremely rare manifestation of a rare disease, makes it an unlikely explanation of the folkloric vampire.[58]. Porphyria is an incurable, inherited disorder that affects the nervous system and skin. Some people may have porphyria, but have it be in remission until lifestyle circumstances change. Donald Trump (1946 - ) Businessman, US President. Only 6 cases of ALAD-deficiency porphyria (ADP) are documented. A drug called Panhematin has been approved for acute versions of Porphyria and it helps to correct the hemoglobin deficiencies that the disorder causes in the liver. One of the more common types of the disease is acute intermittent porphyria (AIP), which famously afflicted the unfortunate King George III of Britain--the "mad king" of Alan Bennetts play. King George IIIPorphyria Portrait of George III of the United Kingdom. "New Light on Medicine," by Nick Lane; Scientific American, January 2003. Longer-acting medications can be . These triggers can be things like: Drinking alcohol. [1] The types that affect the nervous system are also known as acute porphyria, as symptoms are rapid in onset and short in duration. Is there a database for insurance claims? Porphyrias are generally classified into two groups: the hepatic and erythropoietic types. Another relatively common form is porphyria cutanea tardea, which presents a very different spectrum of symptoms. More filters . 3. George III's recurring bouts of illness resulted in withdrawal from society to recuperate out of the public eye at Kew Palace, near Richmond. Diagnosis This is not the main problem in the porphyrias; most heme synthesis enzymeseven dysfunctional enzymeshave enough residual activity to assist in heme biosynthesis. The enzyme (hematin) necessary to alleviate symptoms is not absorbed intact on oral ingestion, and drinking blood would have no beneficial effect on the sufferer. Queen Victoria's III's 2 greats grandson Prince William of Gloucester, (eldest son of Prince Henry, Duke of Gloucester, a son of King George V), a first cousin of the Queen, who died in an air crash in 1972 at the age of 31, was reliably diagnosed with variegate porphyria. These risk factors include: High alcohol consumption Smoking Viral infection (hepatitis C or HIV) Estrogen replacement Iron build up in the body Risk Factors of Porphyria The treatment apparently cures the disease over a period of years. [16], If all the porphyrin studies are negative, one must consider pseudoporphyria. When experiencing a porphyria attack, it is not uncommon for their to be eyesight blurring or other changes that occur because of a dysfunction in the nervous system. In CEP, the genetic fault affects the stem cells in the bone marrow, which divide to produce new red blood cells. 4. Pharmaceutical-grade beta carotene may be used in its treatment. In addition, the folkloric vampire, when unearthed, was always described as looking quite healthy ("as they were in life"), while due to disfiguring aspects of the disease, sufferers would not have passed the exhumation test. Erythropoietic protoporphyria (EPP), the most common kind of porphyria to occur in childhood, causes people's skin to become very sensitive to light. [51], Porphyrias have been detected in all races and in multiple ethnic groups on every continent. Fasting of 24 hours can promote symptom triggers, but intermittent fasting has also shown to be helpful in symptom reduction. The cutaneous porphyrias include the following types: Also called congenital porphyria. William was found to be suffering from fever and cutaneous hepatic symptoms, beginning in December 1965 and lasting several months. People with cutaneous porphyria develop blisters, itching, and swelling of their skin when it is exposed to sunlight. Pain should be treated as early as medically possible. Here's a speculative look at the mental health of 11 of history's big thinkers. These are associated with accumulation of porphyrins in erythrocytes and are rare. Hundreds died, and use of the fugicide was later banned around the world. He was never informed when Queen Charlotte died in 1818. Its sometimes referred to colloquially as vampire disease. Other future treatments for porphyria will depend on the results obtained from research with experimental animal--and even plant--models. Porphyrins and porphyrin precursors and related substances originate in excess amounts predominantly from the liver in the hepatic types and mostly . Some benzodiazepines are safe and, when used in conjunction with newer anti-seizure medications such as gabapentin, offer a possible regimen for seizure control. Explore our digital archive back to 1845, including articles by more than 150 Nobel Prize winners. George III ruled Britain for more than half a century and presided over the Seven Years War and the American Revolution, but throughout his life he also suffered recurring bouts of insanity that left him incapacitated and occasionally confined to a straitjacket. Treatment options are generally to reduce symptoms. Dreamstime is the world`s largest stock photography community. Porphyria cutanea tarda is the name of a song by the rock band AFI on their fourth album Black Sails in the Sunset, released on May 18, 1999. Murray ED, Buttner N, Price BH. Estrogen use by women. Vampires' famed sun-aversion is likely connected to the symptoms of cutaneous porphyrias such as PCT. Porphyrin is necessary for hemoglobin to function properly. Burning. 1970-2011 Drs. It causes blisters in sun-exposed skin areas, excessive scarring, increased hair growth when the skin is exposed to sunlight, and even liver damage. When I was born, I was completely all right. Veterans who have been exposed to Agent Orange have been diagnosed with Porphyria may be diagnosed with up to a 10% disability because of this condition. Thanks for reading Scientific American. All other porphyrias are either skin- or nerve-predominant. Knowledge awaits. One friend wrote that upon witnessing Johnsons gesticulations as he walked down a London street, a group of men, women, and children gathered around him, laughing.. His urine was reported to have been blood red by his physicians. Erythropoietic . Thanks for reading Scientific American. Surprisingly, even plants--which use the green porphyrin, chlorophyll, to absorb light energy--can suffer from a condition analogous to porphyria. In fact, porphyria is sometimes referred to as the "vampyre . Saad postulates that celebrities like Tom Cruise, Justin Bieber, the Kardashians, et al, were narcissists before they became famous. The products of the earlier steps, porphyrin intermediates, may build up to toxic levels. (Put to medical use, drugs containing porphyrins can attack tumors and other ailments. The king Georges III, the lady with the tattoos, Sean Albright - American racecar driver has Variegate Porphyria (VP). Number of people. [1] Symptoms of an attack include abdominal pain, chest pain, vomiting, confusion, constipation, fever, high blood pressure, and high heart rate. It is assumed Mary inherited the disorder from her father, James V of Scotland. Heme function plays a central role in cellular metabolism. "Never go to bed mad. [6] Elevation of aminolevulinic acid from lead-induced disruption of heme synthesis results in lead poisoning having symptoms similar to acute porphyria.[7][8][9][10][11][12]. After 2 months when my mother cut my nails, there was some water. In August 1968, Prince William was examined by Dr. Henry Bellringer, at the request of the his mother, Princess Alice of Gloucester. Charlotte of Mecklenburg-Strelitz PreviousNext The fifteen children of George III, Copyright 2004 - 2022 www.englishmonarchs.co.uk All rights reserved All rights reserved Privacy Policy, Copyright 2004 - 2022 www.englishmonarchs.co.uk All rights reserved All rights reserved . Contemporaries often remarked on the Great Emancipators sorrow. Some drugs are absolutely contraindicated for patients with any form of porphyria. Russell Brand is a British comedian, actor, and activist. The paper diagnosed Steve Jobs with Obsessive Compulsive Personality Disorder (301.4) and Narcissistic Personality Disorder (301.81) with a stand-by diagnosis of Borderline Personality Disorder. [2] Treatment of porphyria of the skin generally involves the avoidance of sunlight, while treatment for acute porphyria may involve giving intravenous heme or a glucose solution. (You probably know him as Vlad the Impaler or Vlad Dracula, the inspiration for Bram Stokers Dracula.) 2 Whoopi Goldberg. Author Joshua Wolf Shenk has even published a full-length book on the subject titled Lincolns Melancholy.. They confidently put forward their claims in a paper in the British Medical Journal entitled "The Insanity of King George III: A Classic Case of Porphyria", which was followed up in 1968 by a further paper "Porphyria in the Royal Houses of Stuart, Hanover and Prussia". [27], The body requires porphyrins to produce heme, which is used to carry oxygen in the blood among other things, but in the porphyrias there is a deficiency (inherited or acquired) of the enzymes that transform the various porphyrins into others, leading to abnormally high levels of one or more of these substances. . Porphyrias are a group of rare inherited blood disorders. Weakness or paralysis, numbness, tingling, and muscle pain are other signs of porphyria. In 1788, however, the king experienced an episode of insanity, believed to be caused by a genetic disease, porphyria, though some historians dispute this . Signs and symptoms. As a result of feedback, the decreased production of heme leads to increased production of precursors, PBG being one of the first substances in the porphyrin synthesis pathway. 6 Acute porphyria, whether symptomatic or not, carries an increased risk of hypertension, hepatocellular carcinoma, and chronic renal failure. Episodes of . Continue reading with a Scientific American subscription. In January 1964, L. Illis's 1963 paper, "On Porphyria and the Aetiology of Werewolves," was published in Proceedings of the Royal Society of Medicine. [5] The underlying mechanism was first described by German physiologist and chemist Felix Hoppe-Seyler in 1871. [2], Patients with the acute porphyrias (AIP, HCP, VP) are at increased risk over their life for hepatocellular carcinoma (primary liver cancer) and may require monitoring. [citation needed] Porphyria cutanea tarda is the disease that both Dabney Pratt and Brother Rush suffer from in Virginia Hamilton 's children's novel Sweet Whispers, Brother Rush. In general, testing involves sending samples of blood, stool, and urine to a reference laboratory. The recommended dietary allowance for carbohydrates is 130 g per day when Porphyria has been diagnosed. In 1816, the author of such beloved novels as Emma and Pride and Prejudice came down with a host of mysterious ailments including exhaustion, back pain, skin discoloration, bilious attacks and fever. Gabapentin has the additional feature of aiding in the treatment of some kinds of neuropathic pain. The blockage of the assembly line also means that the body cannot make enough heme to produce normal red blood cells. Hepatoerythropoietic porphyria creates a greater than 90% deficiency in the needed enzyme. It has been suggested that King George III of Great Britain suffered from the haem biosynthetic disorder, variegate porphyria. Carys O'Neill Chicago, IL Portrait of Queen Victoria with her husband, Albert, and nine children at Osborne circa 1857. Porphyria has since become the most popular explanation for the Kings madness, but in recent years the theory has been criticized by scholars who argue that bi-polar disorder or some other mental illness is the more likely candidate. All porphyrias are generated by enzymes deficit of heme metabolism, leading to an aggregation of porphyrin or its precursors [delta-aminolevulinic acid (ALA) and porphibilinogne (PBG)]. But at the age of six, the Mexican artist was stricken with polio. Occasionally, there may be short-lived psychiatric symptoms such as anxiety, confusion, hallucinations, and, very rarely, overt psychosis. Lincoln dealt with his infrequent breakdowns through humor, but his blue moods later continued during his time in the White House, when he faced the stresses of the Civil War and the untimely death of his 11-year-old son, Willie. Later, in the Byzantine Empire, the term porphyrogenitos, or "born to the purple," literally meant that the imperial heir was born after the fathers accession to the throne, in a palace room draped in the color. Luckily, most people with AIP have a latent form, and never develop any symptoms. People demanded those methods because extravagant cases like the one about Angelo Hays's gained fame. Sometimes, however, the hair growth can give the appearance of a werewolf, leading to speculations that the myths may have had a medical basis. A follow-up study of George 3d's illness", "The Last King of America: The Misunderstood Reign of George III", "bulletin: The University of Sussex NewsletterThe Royal Family's Toxic Time-Bomb Friday 25th June 1999", "BBC News - UK - Charles visits 'relative' Dracula's home", "Vincent van Gogh's illness: acute intermittent porphyria? Defects in any of these can lead to some form of porphyria. One of the more common types of the disease is acute intermittent porphyria (AIP), which famously afflicted the unfortunate King George III of Britainthe mad king of Alan Bennetts play. Which is Clapeyron and Clausius equation? Hello I am from Pakistan. From left to right: Alice, Arthur, Prince Albert, Albert Edward, Leopold, Louise, Queen Victoria with Beatrice, Alfred, Victoria, and Helena. General acute porphyria is more common in women and cutaneous porphyria is more common in men. Porphyria is a group of inherited metabolic disorders, caused of bydifferent faulty genes. King George IIIPorphyria George III ruled Britain for more than half a century and presided over the Seven Years War and the American Revolution, but throughout his life he also suffered recurring bouts of insanity that left him incapacitated and occasionally confined to a straitjacket. 2. Famous cases have been linked to porphyria, such as Prince William of Gloucester, a paternal cousin of the present British Queen Elizabeth II. This is in case they develop severe symptoms, or in case of accidents where there is a potential for drug exposure, and as a result they are unable to explain their condition to healthcare professionals. She experienced headaches and seizures for the rest of her life, but she also showed signs of narcolepsy, a brain condition which can cause rapid and unavoidable bouts of sleep. Macalpine concluded that all those symptoms added up to a mild case of porphyria. The most common erythropoietic porphyria, erythropoietic protoporphyria (EPP), is estimated to have a prevalence rate of 1 in 50,000 to 1 in 75,000. He called the condition pempigus leprosus. Stinging. Historians long hypothesized that his madness may have been due to an undiagnosed family history of porphyria. Porphyria Cutanea Tarda occurs in the Cacausian population at a rate of 1 in 25,000. For the rarest form of the condition (ADP), only six cases have ever been recorded. His friend Henry Whitney noted that, No element of Mr. Lincolns character was so marked, obvious and ingrained as his mysterious and profound melancholy. The severity of Lincolns hypo remains a point of contention among historians today, but many believe that he may have suffered from clinical depression. Public Domain George III ruled Britain for more than half a century and presided over the Seven Years' War and the American. If absolutely necessary, patients should use the medications with the shortest course in case of an attack. In the United Kingdom, supplies of NormoSang are kept at two national centers; emergency supply is available from St Thomas's Hospital, London. Demi Lovato. Porphyria cutanea tarda affects people around the world and isn't limited to a particular region or country. 14. These diseases primarily affect the nervous system, resulting in episodic crises known as acute attacks. This is typical of XLDPP and EPP. These heme-like substances theoretically inhibit ALA synthase and hence the accumulation of toxic precursors. Porphyria had tormented Mary Queen of Scots, who passed it on to her son, King James I of England. Drugs such as barbiturates, tranquilizers, birth control pills, and sedatives are known to trigger the condition. Download Porphyria stock photos. However, even if a mutated gene is inherited, it doesn't guarantee that someone will experience symptoms (this is called latent porphyria). Fewer than 300 cases have been reported in the medical literature of Congenital Eyrthropoeitic Porphyria. Variegate porphyria is most common in South America with an incidence rate that is as high as 3 in every 1,000 people. Following a variable period of, Vesiculo-erosive skin disease. 2023 Scientific American, a Division of Springer Nature America, Inc. 10. Exposure to sunlight is the greatest issue. [citation needed], Cimetidine has also been reported to be effective for acute porphyric crisis and possibly effective for long-term prophylaxis. The porphyrias are a group of disorders connected with the production of haem, which is used to make haemoglobin in red blood cells. This is a rare disorder that mainly affects the skin. The team found further evidence of the ailment in personal correspondence in which the elderly artist complains of gout and notes that he was unable to reply to a letter because my hand refused to write. Michelangelos condition may have been accelerated by the decades of chiseling and painting required to produce such masterpieces as the Pieta, the David and the ceiling of the Sistine Chapel, but the researchers also note that his commitment to hard work may have helped him keep the use of his hands until late in his life. Beethoven was periodically depressed; Tolstoy was a strange, otherworldly, idiosyncratic aristocrat; and lets not forget the periodically outright psychotic, super-genius Isaac Newton. [citation needed], As most porphyrias are rare conditions, general hospital labs typically do not have the expertise, technology, or staff time to perform porphyria testing. Among other descendants of George III claimed to have suffered from porphyria were his granddaughter, Princess Charlotte Augusta of Wales, the only child of George IV and his first cousin, Caroline of Brunswick. Russell Brand is a British comedian, actor, and activist. While the accumulation of porphyrins is usually caused by a genetic mutation, toxins (such as alcohol excess) and environmental contaminants can also cause the disease. This causes local skin damage. This is basically a dramatic monologue written about love and some melodramatic features also can be found here. famous people with porphyria Author: Published on: toyota land cruiser hzj 73 technische daten June 1, 2022 Published in: nymphensittich hat gleichgewichtsstrungen She chaired the British and Irish Porphyria Network from 2008 to 2014. Daytime hours are generally best. Most seizure medications exacerbate this condition. The exception to this may be latent post-puberty genetic carriers of hereditary coproporphyria. It's also called the Vampire disease. The hepatic porphyrias are characterized by acute neurological attacks (seizures, psychosis, extreme back and abdominal pain, and an acute polyneuropathy), while the erythropoietic forms present with skin problems, usually a light-sensitive blistering rash and increased hair growth.Variegate porphyria (also porphyria variegata or mixed porphyria), which results from a partial deficiency in PROTO oxidase, manifests itself with skin lesions similar to those of porphyria cutanea tarda combined with acute neurologic attacks. Mary's symptoms included gastric ulcers, rheumatism and hysteria. In 1810, he suffered a total relapse, from which he was never to recover. This poem published in the year of 1836. Graham Greene. Resolution. Porphyria is an incurable genetic disease, the symptoms of which align perfectly with those ascribed to vampires. Frederick the Great of Prussia (1712 - 1786) a grandson of George I, is believed to have suffered from an acute form of porphyria, like his relative George III. George Clooney, actor and star of movies like "Up in the Air" and the "Ocean's Eleven" series was diagnosed with Bell's palsy when he was a 14. Most kinds of sunscreen are not effective, but SPF-rated long-sleeve shirts, hats, bandanas, and gloves can help. Some people with protoporphyria also develop liver damage and cirrhosis, and up to 5 percent of people with protoporphyria develop liver failure. This means that substances that are made during the process leading up to haem synthesis (including porphyrins) are overproduced and can build up within the body and cause symptoms. Acute porphyrias The most common of these is acute intermittent porphyria. Taking a drug used to treat malaria hydroxychloroquine (Plaquenil) or, less often, chloroquine (Aralen) to absorb excess porphyrins and help your body get rid of them more quickly than usual. The chronicler Plutarch describes Caesar as being afflicted with distemper in the head and notes that he once fell into a fit in which his body trembled, and some of the papers he held dropped out of his hands. Suetonius, meanwhile, says Caesar was struck by a similar sickness on two different occasions during his military campaigns. In principle, CEP can be cured by bone-marrow transplantation, which replaces the faulty stem cells with fully functional ones. I love to write and share science related Stuff Here on my Website. Plants make chlorophyll via a pathway very similar to that for heme production in animals. The exact prevalence of porphyria is unknown, but it likely ranges from 1 in 500 to 1 in 50,000 people worldwide. It is important to note that people who have one type of porphyria do not develop any of the other types. He often . A 1995 article from the Postgraduate Medical Journal (via NIH) explains: As it was believed that the folkloric vampire could move about freely in daylight hours, as opposed to the 20th century variant, congenital erythropoietic porphyria cannot readily explain the folkloric vampire but may be an explanation of the vampire as we know it in the 20th century. Sometimes the spleen must be removed in an attempt to treat the hemolytic anemia. Anemia For instance, the polyneuropathy of acute porphyria may be mistaken for GuillainBarr syndrome, and porphyria testing is commonly recommended in those situations. People with porphyria should, therefore, avoid medications as much as possible, including recreational drugs such as cannabis. Bradley WG, Daroff RB, Fenichel GM, Jankovic J (eds.) Charlotte described in her letters to her physician suffering terrible pains in the abdominal area which wandered around her body, being lame, having blisters all over her face and having dark red urine. Samples must be protected from light and either refrigerated or preserved. Support Porphyria Research. Likewise, people suffering from porphyria will feel constant abdominal pains, will have increased hair growth, bouts of vomits and tightened skin. Famous British People. Heme infusions help in the treatment of porphyria patients in two ways. 5 In people with protoporphyria, bile carries extra porphyrins from the liver to the gallbladder, which may lead to gallstones that are made of porphyrins. . . [31] In nearly all cases of acute porphyria syndromes, urinary PBG is markedly elevated except for the very rare ALA dehydratase deficiency or in patients with symptoms due to hereditary tyrosinemia type I. All these symptoms resolve once the acute attack passes. [1] Rates are different around the world. The recent diagnosis comes from of a group of medical researchers who analyzed portraits of the Renaissance master from different points in his life. Alcohol consumption and cigarette smoking (nicotine use) should be limited. Side effects are rare but can be serious. Felicity helped organise the first BPA Awareness Day in Salford in 2005 and was made a patron in 2012. 13. [citation needed], Any sign of low blood sodium (hyponatremia) or weakness should be treated with the addition of hematin, heme arginate, or even tin mesoporphyrin, as these are signs of impending syndrome of inappropriate antidiuretic hormone (SIADH) or peripheral nervous system involvement that may be localized or severe, progressing to bulbar paresis and respiratory paralysis. Thisa reference to the characteristic, Descendants of George III. This page is currently unavailable. Winston Churchill. He also lives with attention-deficit-hyperactivity-disorder. Frederick the Great of Prussia (1712 - 1786) a grandson of George I, is believed to have suffered from an acute form of porphyria, like his relative George III. Nikola Tesla was often mentally compromised, and Wolfgang Amadeus Mozart suffered from mood swings. A number of psychologists claim that Smith exhibited many of the symptoms of histrionic personality disorder. In the 1960s, researchers combed through the Kings medical records and concluded that he may have suffered from porphyria, a genetic condition that affects the blood and produces such symptoms as abdominal and muscle pain, anxiety, hallucinations and discolored urineall of which George was known to exhibit. Later, Nancy Garden argued for a connection between porphyria and the vampire belief in her 1973 book, Vampires. Thats why having statistics like these on-hand can be so useful. He ruled Walachia, Romania, off and on from 1456-1462.. 6. Second, the extra heme suppresses further heme synthesis via a negative feedback loop. In congenital erythropoietic porphyria (CEP), one of the rarest forms, 18 different mutations in the gene encoding the enzyme uroporphyrinogen III cosynthase have been reported in different families. Vlad Dracul was born in Transylvania, Romania. Extremely rare; fewer than 10 cases ever reported.
