Porphyria Theory
St. Germain's Purple Secret
Though not widely reported, descendants of St. Germain suggest that he suffered from porphyria, a genetic blood disease with symptoms linked to eastern European bloodlines. They know because they share the same inherited health challenges today. Only a DNA analysis could confirm this hypothesis about the mage, but it connects certain dots within his plausible ancestry and biography.
Even without a hypothetical genetic disorder, lead poisoning inhibits porphyrin synthesis and St. Germain's lifelong practice of alchemy and chemistry in dank basements made him prone in old age to pneumonia and poisoning from noxious vapors of mercury and lead. Heavy metals and maybe asbestos can trigger porphyria even without genetic predisposition. He engaged in such activity in his alleged last years at Louisenlund. Latency is common, and some carriers only become symptomatic after exposure to precipitating factors such as alcohol or certain drugs. Is this why St. Germain didn't drink?
Porphyria began at the beginning of time and has continued to mutate throughout ensuing generations. Porphyrins exist abundantly in plants, animals and rocks 1 and have even been found in lunar dust. They existed by the time the first chlorophyll-containing photosynthetic organisms appeared some 3 billion years ago to initiate the creation of a new atmosphere, rich with life-supporting oxygen. Our present ecosystem relies extensively on porphyrins for various vital roles ranging from photosynthesis to oxygen transport, in the form of chlorophyll and heme.
Iron, which is chelated in the center of the heme group, may have been selected instead of another metal for evolutionary reasons, due to its abundance in the crust of earth. Hemoglobin and myoglobin are believed to have emerged more than 600 million years ago. Structurally, hemoglobin consists of four protein subunits, with each subunit associated with a heme group chelated with an iron atom in the center. Its evolution permitted animals to develop complex circulatory systems, which in turn permitted larger organism sizes and higher functions.
The porphyrias are a classification of at least 8 different diseases which are caused by abnormalities in heme production. Heme is part of the hemoglobin in blood that has the ability to carry oxygen. It is a porphyrin molecule which contains iron and gives blood its red color. Also it functions in the liver to break down chemicals so that they can be excreted in the form of urine or in feces.
These are life-long diseases and the symptoms may come and go. Porphyria is not one condition, but a group of diseases. While most of them are inherited, some can be picked up later in life. Acute intermittent porphyria (AIP) is the most common of the forms. Abdominal pain occurs in 90-95% of the attacks. Some patients develop psychiatric symptoms such as psychosis similar to schizophrenia. The diagnostic difficulty may lead to under-diagnosis of patients who present with strictly psychiatric symptoms.
Porphyrias are detected in all 'races.' Jewish ethnicity is linked to Congenital Erythropoietic Porphyria. Cavalli-Sforza in The History and Geography of Human Genes groups people into geographic and evolutionary clusters--but, he writes, ''At no level can clusters be identified with races.'' Types include ALA Dehydratase Porphyria, Porphyria Cutanea Tarda, Congenital Erythropoietic Porphyria, Hepatic Coproporphyria, Erythropoietic Protoporphyria, and Variegate Porphyria. Four of these can sometimes cause sensitivity to light: Erythropoietic Protoporphyria (EPP) or Protoporphyria, Congenital Erythropoietic Porphyria (C.E.P.), Porphyria Cutanea Tarda (PCT) and Variegate Porphyria.
Porphyrias are caused by a build up of particles called porphyrins. These exist in all living things, but in porphyria, the enzyme that processes them breaks down. This causes illness because the porphyrins act as a toxin. Porphyrias have been linked to several diseases including autoimmune diseases, a predisposition to type 2 diabetes and cancers. For fifty years the damage from dominantly inherited porphyrias (PCT, AIP, HCP, VP, EPP) has been noted to trigger transient or sustained autoantibodies evolving to conditions such as lupus erythematosus, rheumatoid arthritis, scleroderma or Sjogren's disease.
Common triggers include:
The porphyrias: The 8 forms of the disease are caused by an incomplete heme enzyme deficiency at some step in the chemical pathway.. Acute intermittent and its variants feature neurotoxicity from delta-amino levulininc acid and porphobilinogen; stomach aches and insanity. Enzyme deficiency is exacerrbated by further inhibiting it with barbiturates or opiates. Cutanea tarda and its worse relatives feature photosensitivity, with scarring, extra hair, and blistering, from buildup of porphyrins themselves. A clinically similar form of porphyria, known as X-Linked dominant protoporphyria, was identified in 2008 and is passed through the maternal line.
Porphyria was more common than elsewhere in small Transylvanian villages roughly 1000 years ago when inbreeding probably occurred. Ironically, it arose in ancient Sun worshipping cultures. The haem group, found in every blood cell in the human body, is excited by electrons, but in a controlled fashion. However, the haem groups in porphyria sufferers causes uncontrollable tissue, bone and skin damage, made worse when the person comes into contact with sunlight.
Porphyria sufferers can have very pallid skin color, with teeth that appear larger than normal, due to the porphyria damaging the gum tissue and causing it to recede. These people would have been very anemic, and drinking (animal) blood was a traditional treatment for anemia. Certain forms of porphyria are also associated with neurological symptoms, which can create psychiatric disorders. However, suggestions that porphyria sufferers crave the heme in human blood, or that the consumption of blood might ease the symptoms of porphyria, are based on misunderstanding and medically-ignorant superstition. Phlebotomy or bloodletting was the treatment of choice for many disorders.
In 1985 David Dolphin, a biochemist, suggested that the mythical vampires might have been people suffering with porphyria. He made his case by pointing out that porphyria victims are exceedingly sensitive to sunlight. Exposure can cause burning of the skin and disfigurements such as scarring, their noses and fingers may wither up and fall off and the lips and gums may tighten up so much that the teeth project like fangs. To avoid sunlight, the sufferers may only go outside after dark and they may install heavy drapes on the windows to keep sunlight out. Also hundreds of years ago, victims might have tried to medicate themselves by drinking blood, and they might have sought out garlic as an herbal remedy but it only makes the porphyria symptoms worse. http://suite101.com/a/porphyria-the-disease-that-created-dracula-a162008
Royal Malady
Vampire legends trace back at least 4000 years to ancient Mesopotamia, the root of all royal lines. The Greeks and Celts had similar creatures in their folklore, and Indian mythology featured shape-shifter vampires who took over dead bodies for their own use. Wandering nomads carried the vampire legends to the Middle East, Asia and Europe.
Hemophilia and porphyria are known throughout the royal bloodlines as the scourge of inbreeding, particularly in the lines of Queen Victoria. The episodic disease is difficult to understand, moreso in past centuries. It can be somewhat controlled by avoiding triggers. It may be that the disease, which can manifest as acute intermittent porphyria (AIP), lay dormant until late life onset.
An attack of acute intermittent porphyria is manifested by a wide range of symptoms. The actual cause of the attack is the absence of an enzyme, porphobilinogen deaminase, that converts a chemical called a porphyrin into heme, a component of hemoglobin, the iron-based chemical in red blood cells that carries oxygen around the body. Porphyrins are toxic to the body in high doses and attacks occur when stress, diet, or something else causes the body to not be able to filter the excess porphyrins. Pain is severe and most often located in the abdomen and the hands and feet (peripheral neuropathy). Often pain needs to be treated with IV morphine or other equally strong narcotics. Insomnia is common. Nausea, vomiting, constipation, and diarrhea all can occur. Muscle weakness, seizures, headaches, forgetfulness and confusion are often the neurological symptoms. The heart races and tachycardia (high heart rate) and hypertension (high blood pressure) are not uncommon even when an attack is not occurring. Psychiatric problems can occur and can sometimes be the only manifestation of the disease. Often individuals afflicted with porphyria are simply depressed and have anxiety issues but in more severe attacks serious cases of paranoia and psychosis can occur. http://oneminutehistory.blogspot.com/
The origins of the disease in the royal family is often attributed to Mary, Queen of Scots and her son, James VI of Scotland and I of England. However, there are indications the condition may have been present as far back as Edward I and may have been introduced into the House of Stuart via Henry VIII’s sister, Margaret Tudor, who married James IV of Scotland. The Stuarts and Hanoverians carried the disorder into Europe through various alliances, and subsequent intermarriages increased the likelihood of the disease being passed down through the generations.
http://www.painted-veil.net/the-curse-of-royal-blood/
Porphyria can be traced through the Stuarts, Tudors, Hanovers, and Katherine of Valois probably brought it from France, where he father Charles VI was a "typical porph" according to some. Some Scots families were followers of the Stuarts before they were Stewards, went from Brittany to England to Scotland with them, and somehow picked up the porphyria gene.
Queen Elizabeth's cousin Duke of Gloucester had it but died without children. Many Stewart monarchs had it, and Elizabeth, daughter of James I/VI probably took it to Germany. It came back with the Hanovers and really got going. Victoria or Albert had it, or both of them, because DNA has been done on bones of Victoria's daughter Vicki and Vicki's Charlotte (see The Purple Secret).
Three academics got permission to open Charlotte's grave. Initially they were told that her remains had been burned by the communists. Then they found her grave, but the German authorities were reluctant to give permission to exhume her. Finally, in 1997, they were allowed to remove the three-tonne slab from her coffin. "There she lay," says John, "with flowers still clutched in her hand." Scraping some bone marrow from her femur, they tested it for porphyria. "She had the disease, beyond a shadow of a doubt," says John, "and the chances of her having it independently from George III are almost impossible." There is a one-in-two chance of any member of the Royal family with the faulty gene passing it on to each offspring. Of that number, around 10% will suffer symptoms. http://www.sussex.ac.uk/internal/bulletin/archive/25jun99/article1.html
It is a dominant gene and affects 50% of children, but is recessive in very rare forms. So there are no "carriers" except that some men are able to not "show" it--because not triggered, and thus could pass it on. It is dominant, so that 50% of children get it on one parent's line, and if two parents have it, 75% (on average). The only way a person can be thought to be a carrier (unlike hemophilia) is if that person has the gene but it is not triggered into disease, which happens frequently.
The disease affected the royals before the Hanover arrival. James I/VI is thought to have gotten it from Mary Queen of Scots and/or Lord Darnley. Lord Darnley had both Stewart and Tudor genes but also the Tudor genes. It is suggested that the Tudors became active with porphyria through Katherine of Valois, who married first Henry V and then Owen Tudor. Katherine is not written up as "mad", but her father Charles VI of France was actually more often "mad" than George III. He did terrible things such as kill his aides, and then fall into sorrow over what he'd done when he recovered his right mind. He thought he was made of glass and could break. He came from a very inbred line, and his wife Isabeau may have had it as well. Thus Katherine had a very high chance of having it. However, in these old cases, there are no "lab tests" as there are now since the 21th century.
Porphyria is "a group of inherited disorders involving abnormalities in the production of heme pigments (the base material responsible for hemoglobin (red blood cell pigment), myoglobin (reddish muscle cell pigment) and another group of materials called cytochromes." (From http://health.allrefer.com/health/porphyria-info.html#definition)
It may account for some of St. Germain's enigmatic behaviors, such as never eating in the company of others. Even today, those with the condition are often reduced to eating only the most benign of foods, such as organic oatmeal or porridges. So, naturally he may have had to pass up gluttonous royal feasts. They can be highly sensitive to the sun, erupting in skin lesions with overexposure, and prone to seizures and even deep comas, which might in the past have been mistaken for death. Severity varies with each individual; not everyone will display the whole range of symptoms, which depend also on the type of porphyria.
There is no escape from light when outside for those with the rare light intolerance disorder Erythropoietic Protoporphyria (EPP). It demands a shadowy existence. Facial skin lesions can lead to a monstrous appearance. The gums pull back exaggerating a fang-like grimace. https://vimeo.com/8302697
Such disorders are often hidden because they were enmeshed with legends of vampiric behavior. Vampire legends are most closely associated with Transylvanian royal lines. Symptoms became overlaid with myth. A quick scan of the symptoms and behaviors reveals why this might be so. It may even be that medieval family remedies included the drinking of animal blood. Perhaps it motivated the mage's search for healing elixirs. Video: https://vimeo.com/23267877
Porphyria symptoms and signs include:
http://health.allrefer.com/health/po...-symptoms.html
http://porphbook.tripod.com/8.html
Genetics
A number of disease-specific mutations have been identified in each of the genes that encode the enzymes that are deficient in the porphyrias.
Porphyria symptoms and signs include:
http://health.allrefer.com/health/po...-symptoms.html
http://porphbook.tripod.com/8.html
Even without a hypothetical genetic disorder, lead poisoning inhibits porphyrin synthesis and St. Germain's lifelong practice of alchemy and chemistry in dank basements made him prone in old age to pneumonia and poisoning from noxious vapors of mercury and lead. Heavy metals and maybe asbestos can trigger porphyria even without genetic predisposition. He engaged in such activity in his alleged last years at Louisenlund. Latency is common, and some carriers only become symptomatic after exposure to precipitating factors such as alcohol or certain drugs. Is this why St. Germain didn't drink?
- Latency is common and there can be asymptomatic or minimally symptomatic carriers. Some carriers only
become symptomatic after exposure to an additional agent or factor capable of inducing disease expression.
Porphyria began at the beginning of time and has continued to mutate throughout ensuing generations. Porphyrins exist abundantly in plants, animals and rocks 1 and have even been found in lunar dust. They existed by the time the first chlorophyll-containing photosynthetic organisms appeared some 3 billion years ago to initiate the creation of a new atmosphere, rich with life-supporting oxygen. Our present ecosystem relies extensively on porphyrins for various vital roles ranging from photosynthesis to oxygen transport, in the form of chlorophyll and heme.
Iron, which is chelated in the center of the heme group, may have been selected instead of another metal for evolutionary reasons, due to its abundance in the crust of earth. Hemoglobin and myoglobin are believed to have emerged more than 600 million years ago. Structurally, hemoglobin consists of four protein subunits, with each subunit associated with a heme group chelated with an iron atom in the center. Its evolution permitted animals to develop complex circulatory systems, which in turn permitted larger organism sizes and higher functions.
The porphyrias are a classification of at least 8 different diseases which are caused by abnormalities in heme production. Heme is part of the hemoglobin in blood that has the ability to carry oxygen. It is a porphyrin molecule which contains iron and gives blood its red color. Also it functions in the liver to break down chemicals so that they can be excreted in the form of urine or in feces.
These are life-long diseases and the symptoms may come and go. Porphyria is not one condition, but a group of diseases. While most of them are inherited, some can be picked up later in life. Acute intermittent porphyria (AIP) is the most common of the forms. Abdominal pain occurs in 90-95% of the attacks. Some patients develop psychiatric symptoms such as psychosis similar to schizophrenia. The diagnostic difficulty may lead to under-diagnosis of patients who present with strictly psychiatric symptoms.
Porphyrias are detected in all 'races.' Jewish ethnicity is linked to Congenital Erythropoietic Porphyria. Cavalli-Sforza in The History and Geography of Human Genes groups people into geographic and evolutionary clusters--but, he writes, ''At no level can clusters be identified with races.'' Types include ALA Dehydratase Porphyria, Porphyria Cutanea Tarda, Congenital Erythropoietic Porphyria, Hepatic Coproporphyria, Erythropoietic Protoporphyria, and Variegate Porphyria. Four of these can sometimes cause sensitivity to light: Erythropoietic Protoporphyria (EPP) or Protoporphyria, Congenital Erythropoietic Porphyria (C.E.P.), Porphyria Cutanea Tarda (PCT) and Variegate Porphyria.
Porphyrias are caused by a build up of particles called porphyrins. These exist in all living things, but in porphyria, the enzyme that processes them breaks down. This causes illness because the porphyrins act as a toxin. Porphyrias have been linked to several diseases including autoimmune diseases, a predisposition to type 2 diabetes and cancers. For fifty years the damage from dominantly inherited porphyrias (PCT, AIP, HCP, VP, EPP) has been noted to trigger transient or sustained autoantibodies evolving to conditions such as lupus erythematosus, rheumatoid arthritis, scleroderma or Sjogren's disease.
Common triggers include:
- Drugs (barbiturates and sulfonamide antibiotics, but tranquilizers, birth control pills and sedatives also may cause symptoms; or drug reaction to cancer treatment)
- Dieting or fasting
- Smoking
- Infections or other physical stress
- Stress
- Alcohol use
- Menstrual hormones
- Sun exposure
- Excess iron in your body
The porphyrias: The 8 forms of the disease are caused by an incomplete heme enzyme deficiency at some step in the chemical pathway.. Acute intermittent and its variants feature neurotoxicity from delta-amino levulininc acid and porphobilinogen; stomach aches and insanity. Enzyme deficiency is exacerrbated by further inhibiting it with barbiturates or opiates. Cutanea tarda and its worse relatives feature photosensitivity, with scarring, extra hair, and blistering, from buildup of porphyrins themselves. A clinically similar form of porphyria, known as X-Linked dominant protoporphyria, was identified in 2008 and is passed through the maternal line.
Porphyria was more common than elsewhere in small Transylvanian villages roughly 1000 years ago when inbreeding probably occurred. Ironically, it arose in ancient Sun worshipping cultures. The haem group, found in every blood cell in the human body, is excited by electrons, but in a controlled fashion. However, the haem groups in porphyria sufferers causes uncontrollable tissue, bone and skin damage, made worse when the person comes into contact with sunlight.
Porphyria sufferers can have very pallid skin color, with teeth that appear larger than normal, due to the porphyria damaging the gum tissue and causing it to recede. These people would have been very anemic, and drinking (animal) blood was a traditional treatment for anemia. Certain forms of porphyria are also associated with neurological symptoms, which can create psychiatric disorders. However, suggestions that porphyria sufferers crave the heme in human blood, or that the consumption of blood might ease the symptoms of porphyria, are based on misunderstanding and medically-ignorant superstition. Phlebotomy or bloodletting was the treatment of choice for many disorders.
In 1985 David Dolphin, a biochemist, suggested that the mythical vampires might have been people suffering with porphyria. He made his case by pointing out that porphyria victims are exceedingly sensitive to sunlight. Exposure can cause burning of the skin and disfigurements such as scarring, their noses and fingers may wither up and fall off and the lips and gums may tighten up so much that the teeth project like fangs. To avoid sunlight, the sufferers may only go outside after dark and they may install heavy drapes on the windows to keep sunlight out. Also hundreds of years ago, victims might have tried to medicate themselves by drinking blood, and they might have sought out garlic as an herbal remedy but it only makes the porphyria symptoms worse. http://suite101.com/a/porphyria-the-disease-that-created-dracula-a162008
Royal Malady
Vampire legends trace back at least 4000 years to ancient Mesopotamia, the root of all royal lines. The Greeks and Celts had similar creatures in their folklore, and Indian mythology featured shape-shifter vampires who took over dead bodies for their own use. Wandering nomads carried the vampire legends to the Middle East, Asia and Europe.
Hemophilia and porphyria are known throughout the royal bloodlines as the scourge of inbreeding, particularly in the lines of Queen Victoria. The episodic disease is difficult to understand, moreso in past centuries. It can be somewhat controlled by avoiding triggers. It may be that the disease, which can manifest as acute intermittent porphyria (AIP), lay dormant until late life onset.
An attack of acute intermittent porphyria is manifested by a wide range of symptoms. The actual cause of the attack is the absence of an enzyme, porphobilinogen deaminase, that converts a chemical called a porphyrin into heme, a component of hemoglobin, the iron-based chemical in red blood cells that carries oxygen around the body. Porphyrins are toxic to the body in high doses and attacks occur when stress, diet, or something else causes the body to not be able to filter the excess porphyrins. Pain is severe and most often located in the abdomen and the hands and feet (peripheral neuropathy). Often pain needs to be treated with IV morphine or other equally strong narcotics. Insomnia is common. Nausea, vomiting, constipation, and diarrhea all can occur. Muscle weakness, seizures, headaches, forgetfulness and confusion are often the neurological symptoms. The heart races and tachycardia (high heart rate) and hypertension (high blood pressure) are not uncommon even when an attack is not occurring. Psychiatric problems can occur and can sometimes be the only manifestation of the disease. Often individuals afflicted with porphyria are simply depressed and have anxiety issues but in more severe attacks serious cases of paranoia and psychosis can occur. http://oneminutehistory.blogspot.com/
The origins of the disease in the royal family is often attributed to Mary, Queen of Scots and her son, James VI of Scotland and I of England. However, there are indications the condition may have been present as far back as Edward I and may have been introduced into the House of Stuart via Henry VIII’s sister, Margaret Tudor, who married James IV of Scotland. The Stuarts and Hanoverians carried the disorder into Europe through various alliances, and subsequent intermarriages increased the likelihood of the disease being passed down through the generations.
http://www.painted-veil.net/the-curse-of-royal-blood/
Porphyria can be traced through the Stuarts, Tudors, Hanovers, and Katherine of Valois probably brought it from France, where he father Charles VI was a "typical porph" according to some. Some Scots families were followers of the Stuarts before they were Stewards, went from Brittany to England to Scotland with them, and somehow picked up the porphyria gene.
Queen Elizabeth's cousin Duke of Gloucester had it but died without children. Many Stewart monarchs had it, and Elizabeth, daughter of James I/VI probably took it to Germany. It came back with the Hanovers and really got going. Victoria or Albert had it, or both of them, because DNA has been done on bones of Victoria's daughter Vicki and Vicki's Charlotte (see The Purple Secret).
Three academics got permission to open Charlotte's grave. Initially they were told that her remains had been burned by the communists. Then they found her grave, but the German authorities were reluctant to give permission to exhume her. Finally, in 1997, they were allowed to remove the three-tonne slab from her coffin. "There she lay," says John, "with flowers still clutched in her hand." Scraping some bone marrow from her femur, they tested it for porphyria. "She had the disease, beyond a shadow of a doubt," says John, "and the chances of her having it independently from George III are almost impossible." There is a one-in-two chance of any member of the Royal family with the faulty gene passing it on to each offspring. Of that number, around 10% will suffer symptoms. http://www.sussex.ac.uk/internal/bulletin/archive/25jun99/article1.html
It is a dominant gene and affects 50% of children, but is recessive in very rare forms. So there are no "carriers" except that some men are able to not "show" it--because not triggered, and thus could pass it on. It is dominant, so that 50% of children get it on one parent's line, and if two parents have it, 75% (on average). The only way a person can be thought to be a carrier (unlike hemophilia) is if that person has the gene but it is not triggered into disease, which happens frequently.
The disease affected the royals before the Hanover arrival. James I/VI is thought to have gotten it from Mary Queen of Scots and/or Lord Darnley. Lord Darnley had both Stewart and Tudor genes but also the Tudor genes. It is suggested that the Tudors became active with porphyria through Katherine of Valois, who married first Henry V and then Owen Tudor. Katherine is not written up as "mad", but her father Charles VI of France was actually more often "mad" than George III. He did terrible things such as kill his aides, and then fall into sorrow over what he'd done when he recovered his right mind. He thought he was made of glass and could break. He came from a very inbred line, and his wife Isabeau may have had it as well. Thus Katherine had a very high chance of having it. However, in these old cases, there are no "lab tests" as there are now since the 21th century.
Porphyria is "a group of inherited disorders involving abnormalities in the production of heme pigments (the base material responsible for hemoglobin (red blood cell pigment), myoglobin (reddish muscle cell pigment) and another group of materials called cytochromes." (From http://health.allrefer.com/health/porphyria-info.html#definition)
It may account for some of St. Germain's enigmatic behaviors, such as never eating in the company of others. Even today, those with the condition are often reduced to eating only the most benign of foods, such as organic oatmeal or porridges. So, naturally he may have had to pass up gluttonous royal feasts. They can be highly sensitive to the sun, erupting in skin lesions with overexposure, and prone to seizures and even deep comas, which might in the past have been mistaken for death. Severity varies with each individual; not everyone will display the whole range of symptoms, which depend also on the type of porphyria.
There is no escape from light when outside for those with the rare light intolerance disorder Erythropoietic Protoporphyria (EPP). It demands a shadowy existence. Facial skin lesions can lead to a monstrous appearance. The gums pull back exaggerating a fang-like grimace. https://vimeo.com/8302697
Such disorders are often hidden because they were enmeshed with legends of vampiric behavior. Vampire legends are most closely associated with Transylvanian royal lines. Symptoms became overlaid with myth. A quick scan of the symptoms and behaviors reveals why this might be so. It may even be that medieval family remedies included the drinking of animal blood. Perhaps it motivated the mage's search for healing elixirs. Video: https://vimeo.com/23267877
Porphyria symptoms and signs include:
http://health.allrefer.com/health/po...-symptoms.html
http://porphbook.tripod.com/8.html
Genetics
- The seven porphyrias form a group of inherited metabolic disorders, with the most common being porphyria cutanea tarda
- The majority (80%) of patients have the sporadic (type 1) form of porphyria cutanea tarda, in which UROD deficiency is restricted to the liver
- Familial (type 2) porphyria cutanea tarda accounts for approx. 20%, and may be distinguished from the sporadic cases by measuring erythrocyte UROD activity or by molecular analysis of the UROD gene
- Four additional porphyrias (acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and erythropoietic protoporphyria) are mainly inherited in an autosomal dominant manner, although more complex patterns of inheritance are seen in some families
- The two autosomal recessive porphyrias, congenital erythropoietic porphyria and delta-aminolevulinic acid dehydratase deficiency porphyria, are very rare
A number of disease-specific mutations have been identified in each of the genes that encode the enzymes that are deficient in the porphyrias.
- Gene testing identifies mutations in 90% or more of affected individuals with the various inherited forms of porphyria
- Additional modifier genes, such as the HFE gene for hemochromatosis, are associated with some forms of porphyria, in particular porphyria cutanea tarda
Porphyria symptoms and signs include:
http://health.allrefer.com/health/po...-symptoms.html
http://porphbook.tripod.com/8.html
Red urine (sometimes called purple)
Sensitivity to sunlight Blister formation on exposure to sunlight Skin swelling on exposure to sunlight Photodermatitis Edema Crampy abdominal pain (may be severe) Constipation; diaharrea Vomiting, Dry Heaves Pain in the limbs; neuropathy High blood pressure &Tachycardia Electrolyte imbalances, low blood pressure & shock Bone hypomineralization, dental enamel defects missing adult teeth |
Personality change
Numbness or tingling Muscle pain Muscle weakness or paralysis "Hypertrichosis": increased fine hair growth Scarring; disfigurement Chronic Pain Celiac disease Blindness Insomnia Depression, Anxiety, Paranoia, Psychosis Chemical Sensitivity Coma Catatonia |
Classification (from most to least common type):
Can also be categorized as
Acute porphyrias (delta-aminolevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria, variegate porphyria, hereditary coproporphyria), which typically cause neuropsychiatric problems, often manifesting as a severe abdominal pain and are associated with excess production and excretion in urine of porphobilinogen and delta-aminolevulinic acid
The other five porphyrias are mainly inherited in an autosomal dominant manner, although more complex patterns of inheritance are possible.
Further variation is seen in porphyria cutanea tarda, the most common porphyria worldwide, and many risk factors precipitate the disease.
There are three clinically indistinguishable subtypes:
Type 1 (sporadic, no family history of porphyria) accounts for 80% of cases. UROD activity is inhibited (inactivated) only in the liver. Although sporadic cases do not have mutation in the UROD gene, there is association with mutations in the hemochromatosis (HFE) gene and other, as yet unknown, genetic causes. The disease is precipitated by various risk factors:
Contributory or predisposing factorsAll porphyrias:
References
Schneider-Yin X, Mamet R, Minder EI, Schoenfeld N:
Biochemical and molecular diagnosis of erythropoietic protoporphyria in an Ashkenazi Jewish family. J Inherit Metab Dis 2008,
"The Insanity of King George III: A Classic Case of Porphyria", with a follow-up in 1968, "Porphyria in the Royal Houses of Stuart, Hanover and Prussia".
- Porphyria cutanea tarda (includes hepatoerythropoietic porphyria, a very rare type of porphyria associated with hemolytic anemia)
- Acute intermittent porphyria
- Erythropoietic protoporphyria
- Variegate porphyria
- Hereditary coproporphyria
- Congenital erythropoietic porphyria
- Aminolevulinic acid dehydratase deficiency
Can also be categorized as
- Hepatic porphyrias (delta-aminolevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, porphyria cutanea tarda), in which the excess porphyrin production occurs in the liver
- Erythropoietic porphyrias (erythropoietic protoporphyria, congenital erythropoietic porphyria), in which excess porphyrin production occurs in the bone marrow
Acute porphyrias (delta-aminolevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria, variegate porphyria, hereditary coproporphyria), which typically cause neuropsychiatric problems, often manifesting as a severe abdominal pain and are associated with excess production and excretion in urine of porphobilinogen and delta-aminolevulinic acid
- Nonacute porphyrias (porphyria cutanea tarda, congenital erythropoietic porphyria, erythropoietic protoporphyria), in which porphobilinogen and delta-aminolevulinic acid are not produced in excess
- Autosomal dominant (acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, porphyria cutanea tarda (20% of cases are autosomal dominant), erythropoietic protoporphyria)
- Autosomal recessive (delta-aminolevulinic acid dehydratase deficiency porphyria, congenital erythropoietic porphyria)
https://www.clinicalkey.com/topics/hematology/porphyria.html
- Delta-aminolevulinic acid dehydratase deficiency causes delta-aminolevulinic acid dehydratase deficiency porphyria
- Porphobilinogen deaminase deficiency causes acute intermittent porphyria
- Uroporphyrinogen III synthase deficiency causes congenital erythropoietic porphyria
- Uroporphyrinogen decarboxylase deficiency (UROD) causes the familial type (approx. 20% of cases) and sporadic type (80%) of porphyria cutanea tarda
- Coproporphyrinogen oxidase deficiency causes hereditary coproporphyria
- Protoporphyrinogen oxidase deficiency causes variegate porphyria
- Ferrochelatase deficiency causes erythropoietic protoporphyria
The other five porphyrias are mainly inherited in an autosomal dominant manner, although more complex patterns of inheritance are possible.
- Signature feature for each is low clinical penetrance
- Inheritance of one copy of a mutant gene decreases enzyme activity by 50%, which is sufficient for normal cellular metabolism
- Clinical presentation requires additional factors (genetic or environmental) that affect the heme pathway
- These factors either increase the normal demand for heme production, cause a decrease in enzyme activity, or are a combination of these effects
Further variation is seen in porphyria cutanea tarda, the most common porphyria worldwide, and many risk factors precipitate the disease.
There are three clinically indistinguishable subtypes:
Type 1 (sporadic, no family history of porphyria) accounts for 80% of cases. UROD activity is inhibited (inactivated) only in the liver. Although sporadic cases do not have mutation in the UROD gene, there is association with mutations in the hemochromatosis (HFE) gene and other, as yet unknown, genetic causes. The disease is precipitated by various risk factors:
- Hepatitis C infection
- Alcohol
- Oral estrogens
- Hexachlorobenzene and tetrachloridibenzo-p-dioxin
- Hepatic tumors
- Distinguished from sporadic cases by measuring erythrocyte UROD activity or by molecular analysis
- Coinheritance of UROD mutation and either homozygous or heterozygous HFE C282Y and H63D mutations result in earlier onset of symptoms
- Manifestation of disease requires precipitating factors, such as chronic exposure to alcohol, hepatotropic viruses, excess iron intake or storage, and oral estrogen use
- Additional modifying genetic loci are implicated in the disease process
Contributory or predisposing factorsAll porphyrias:
- Liver disease
- Hepatitis C
- Infection
- Heavy alcohol use
- Major surgery
- Drugs: estrogen and progesterone from contraception and hormone replacement therapies (although may be beneficial in some patients in prevention of cyclic menstrual attacks); danazol; griseofulvin; rifampin, sulfonamides, chloramphenicol and primidone; diclofenac; phenobarbital, carbamazepine, valproic acid, clonazepam, chlordiazepoxide and meprobamate; imipramine; chlorpropamide and metoclopramide; methyldopa and glutethimide; ergotamine; pyrazinamide; carisoprodol; ethchlorvynol; and pentazocine, mephenytoin, succinimides, and pyrazolones
- Steroids: endogenous steroid hormones, sex steroid preparations
- Menstrual cycle: in presence of high levels of progesterone
- Pregnancy
- Fasting
- Emotional and physical stress
- Substance abuse: particularly marijuana, ecstasy, amphetamines, and cocaine
- Tobacco
References
Schneider-Yin X, Mamet R, Minder EI, Schoenfeld N:
Biochemical and molecular diagnosis of erythropoietic protoporphyria in an Ashkenazi Jewish family. J Inherit Metab Dis 2008,
"The Insanity of King George III: A Classic Case of Porphyria", with a follow-up in 1968, "Porphyria in the Royal Houses of Stuart, Hanover and Prussia".
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FAIR USE NOTICE
This site may contains some copyrighted material which has not been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding and knowledge through educational issues. This constitutes a 'fair use' of any such copyrighted material as provided for in section 107 of the US Copyright Law, in accordance with Title 17 U.S.C. Section 107. The material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.
The owners and publishers of these pages wish to state that the material presented here that is the product of our research is offered with the caveat that the reader ought always to research on their own. We invite the reader to share in our Seeking of Truth by reading with an Open, but skeptical mind. We constantly seek to validate and/or refine what we understand to be either possible or probable or both. We do this in the sincere hope that all of mankind will benefit, if not now, then at some point in one of our probable futures. If you wish to use copyrighted material from this site for purposes of your own that go beyond 'fair use', you must obtain permission from the copyright owner