porphyria

por·phyr·i·a

(pôr-fîr'ē-ə) pronunciation

n.
Any of several disorders of porphyrin metabolism, usually hereditary, characterized by the presence of large amounts of porphyrins in the blood and urine.

[New Latin : PORPHYR(IN) + -IA¹.]

porphyric por·phyr'ic adj.

Search unanswered questions...

Browse: Unanswered questions | Most-recent questions | Reference library

porphyria

Top

What made King Geoge III so very mad? The British ruler who presided over the loss of the American colonies in 1776 was diagnosed about two centuries too late with porphyria — a genetic disorder that causes psychiatric disturbances, among other things — and more recently researchers found arsenic in his hair (presumably from contaminated medication), which may have made him even madder:

"'It is extremely likely that his bouts of madness were due to severe porphyric attacks,' [biochemist Martin J.] Warren said. 'Arsenic may have precipitated his attacks, or made them much more severe.'"

Link: Arsenic Is Linked to British King's Episodes of Madness

Posted July 24, 2005.

See our Word Overheard blog to see interesting uses of strange words.

Gale Encyclopedia of Children's Health:

Porphyrias

Top

Definition

The porphyrias are disorders in which the body produces too much porphyrin and insufficient heme (an iron-containing nonprotein portion of the hemoglobin molecule). Porphyrin is a foundation structure for heme and certain enzymes. Excess porphyrins are excreted as waste in urine and stool. Overproduction and overexcretion of porphyrins causes low, unhealthy levels of heme and certain important enzymes, creating various physical symptoms.

Description

Biosynthesis of heme is a multistep process that begins with simple molecules and ends with a large, complex heme molecule. Each step of the chemical pathway is directed by its own task-specific protein, called an enzyme. As a heme precursor molecule moves through each step, an enzyme modifies the precursor in some way. If a precursor molecule is not modified, it cannot proceed to the next step, causing a buildup of that specific precursor.

This situation is the main characteristic of the porphyrias. Owing to a defect in one of the enzymes of the heme biosynthesis pathway, protoporphyrins or porphyrins (heme precursors) are prevented from proceeding further along the pathway. These precursors accumulate at the stage of the enzyme defect, causing an array of physical symptoms in an affected child. Specific symptoms depend on the point at which heme biosynthesis is blocked and which precursors accumulate. In general, the porphyrias primarily affect the skin and the nervous system. Symptoms can be debilitating or life threatening in some cases. Porphyria is most commonly an inherited condition. It can also, however, be acquired after exposure to poisonous substances.

Heme

Heme is produced in several tissues in the body, but its primary biosynthesis sites are the liver and the bone marrow. Heme synthesis for immature red blood cells, namely the erythroblasts and the reticulocytes, occurs in the bone marrow.

Although production is concentrated in the liver and bone marrow, heme is utilized in various capacities in virtually every tissue in the body. In most cells, heme is a key building block in the construction of factors that oversee metabolism and transport of oxygen and energy. In the liver, heme is a component of several vital enzymes, particularly cytochrome P450. Cytochrome P450 is involved in the metabolism of chemicals, vitamins, fatty acids, and hormones; it is very important in transforming toxic substances into easily excretable materials. In immature red blood cells, heme is the featured component of hemoglobin. Hemoglobin is the red pigment that gives red blood cells their characteristic color and their essential ability to transport oxygen.

Heme Biosynthesis

The heme molecule is composed of porphyrin and an iron atom. Much of the heme biosynthesis pathway is dedicated to constructing the porphyrin molecule. Porphyrin is a large molecule shaped like a four-leaf clover. An iron atom is placed at its center point in the last step of heme biosynthesis.

The production of heme may be compared to a factory assembly line. At the start of the line, raw materials are fed into the process. At specific points along the line, an addition or adjustment is made to further development. Once additions and adjustments are complete, the final product rolls off the end of the line.

The heme "assembly line" is an eight-step process, requiring eight different and properly functioning enzymes:

delta-aminolevulinic acid synthase
delta-aminolevulinic acid dehydratase
porphobilogen deaminase
uroporphyrinogen III cosynthase
uroporphyrinogen decarboxylase
coproporphyrinogen oxidase
protoporphyrinogen oxidase
ferrochelatase

The control of heme biosynthesis is complex. Various chemical signals can trigger increased or decreased production. These signals can affect the enzymes themselves or the production of these enzymes, starting at the genetic level. For example, one point at which heme biosynthesis may be controlled is at the first step. When heme levels are low, greater quantities of delta-aminolevulinic acid (ALA) synthase are produced. As a result, larger quantities of heme precursors are fed into the biosynthesis pathway to step up heme production.

Porphyrias

Under normal circumstances, when heme concentrations are at an appropriate level, precursor production decreases. However, a glitch in the biosynthesis pathway—represented by a defective enzyme—means that heme biosynthesis does not reach completion. Because heme levels remain low, the synthesis pathway continues to churn out precursor molecules in an attempt to correct the heme deficit.

The net effect of this continued production is an abnormal accumulation of precursor molecules and development of some type of porphyria. Each type of porphyria corresponds with a specific enzyme defect and an accumulation of the associated precursor. Although there are eight steps in heme biosynthesis, there are only seven types of porphyrias; a defect in ALA synthase activity does not have a corresponding porphyria.

Enzymes involved in heme biosynthesis display subtle, tissue-specific variations; therefore, heme biosynthesis may be impeded in the liver, but normal in the immature red blood cells, or vice versa. Incidence of porphyria varies widely between types and occasionally by geographic location. Although certain porphyrias are more common than others, their greater frequency is only relative to other types. All porphyrias are considered to be rare disorders.

In the past, the porphyrias were divided into two general categories based on the location of the porphyrin production. Porphyrias affecting heme biosynthesis in the liver were referred to as hepatic porphyrias. Porphyrias that affect heme biosynthesis in immature red blood cells were referred to as erythropoietic porphyries. (Erythropoiesis is the process through which red blood cells are produced.) As of 2001, porphyrias are usually grouped into acute and non-acute types. Acute porphyrias produce severe attacks of pain and neurological effects. Non-acute porphyrias present as chronic diseases.

The acute porphyrias, and the heme biosynthesis steps at which enzyme defects occur, are:

ALA dehydratase deficiency porphyria (step 2). This porphyria type is very rare. The inheritance pattern appears to be autosomal recessive. In autosomal recessively inherited disorders, a child must inherit two defective genes, one from each parent. A parent with only one gene for an autosomal recessive disorder does not display symptoms of the disease.
Acute intermittent porphyria (step 3). Acute intermittent porphyria (AIP) is also known as Swedish porphyria, pyrroloporphyria, and intermittent acute porphyria. AIP is inherited as an autosomal dominant trait, which means that only one copy of the defective gene needs to be present for the disorder to occur. Simply inheriting this gene, however, does not necessarily mean that a child will develop the disease. Approximately five to 10 per 100,000 children in the United States carry a gene for AIP, but only 10 percent of these people, mostly teenage or older, ever develop symptoms of the disease.
Hereditary coproporphyria (step 6). Hereditary coproporphyria (HCP) is inherited in an autosomal dominant manner. As with all porphyrias, it is an uncommon ailment. By 1977, only 111 cases of HCP were recorded; in Denmark, the estimated incidence is two in one million people.
Variegate porphyria (step 7). Variegate porphyria (VP) is also known as porphyria variegata, protocoproporphyria, South African genetic porphyria, and Royal malady (supposedly King George III of England and Mary, Queen of Scots, suffered from VP). VP is inherited in an autosomal dominant manner and is especially prominent in South Africans of Dutch descent. Among that population, the incidence is approximately three in 1,000 persons. It is estimated that there are 10,000 cases of VP in South Africa. Interestingly, it appears that the affected South Africans are descendants of two Dutch settlers who came to South Africa in 1680. Among other populations, the incidence of VP is estimated to be one to two cases per 100,000 persons.

The non-acute porphyrias, and the steps of heme biosynthesis at which they occur, are:

Congenital erythropoietic porphyria (step 4). Congenital erythropoietic porphyria (CEP) is also called Gunther's disease, erythropoietic porphyria, congenital porphyria, congenital hematoporphyria, and erythropoietic uroporphyria. CEP is inherited in an autosomal recessive manner. It is a rare disease, estimated to affect fewer than one in one million people. Onset of dramatic symptoms usually occurs in infancy, but may hold off until adulthood.
Porphyria cutanea tarda (step 5). Porphyria cutanea tarda (PCT) is also called symptomatic porphyria, porphyria cutanea symptomatica, and idiosyncratic porphyria. PCT may be acquired, typically as a result of disease (especially hepatitis C), drug or alcohol use, or exposure to certain poisons. PCT may also be inherited as an autosomal dominant disorder, however most people remain latent—that is, symptoms never develop. PCT is the most common of the porphyrias, but the incidence of PCT is not well defined. However, PCT does not typically develop in children.
Hepatoerythopoietic porphyria (step 5). Hepatoerythopoietic porphyria (HEP) affects heme biosynthesis in both the liver and the bone marrow. HEP results from a defect in uroporphyrinogen decarboxylase activity (step 5), and is caused by defects in the same gene as PCT. Disease symptoms, however, strongly resemble congenital erythropoietic porphyria. HEP seems to be inherited in an autosomal recessive manner.
Erythropoietic protoporphyria (step 8). Also known as protoporphyria and erythrohepatic protoporphyria, erythropoietic protoporphyria (EPP) is more common than CEP; more than 300 cases have been reported. In these cases, onset of symptoms typically occurred in childhood.

Causes and Symptoms

General Characteristics

The underlying cause of all porphyrias is a defective enzyme important to the heme biosynthesis pathway. Porphyrias are inheritable conditions. In virtually all cases of porphyria, an inherited factor causes the enzyme's defect. An environmental trigger—such as diet, drugs, or sun exposure—may be necessary before any symptoms develop. In many cases, symptoms do not develop. These asymptomatic individuals may be completely unaware that they have a gene for porphyria.

All of the hepatic porphyrias—except porphyria cutanea tarda—follow a pattern of acute attacks separated by periods during which no symptoms are present. For this reason, this group is often referred to as the acute porphyrias. The erythropoietic porphyrias and porphyria cutanea tarda do not follow this pattern and are considered to be chronic conditions.

The specific symptoms of each porphyria vary based on which enzyme is affected and whether that enzyme occurs in the liver or in the bone marrow. The severity of symptoms can vary widely, even within the same type of porphyria. If the porphyria becomes symptomatic, the common factor between all types is an abnormal accumulation of protoporphyrins or porphyrin.

Ala Dehydratase Porphyria (ADP)

ADP is characterized by a deficiency of ALA dehydratase. ADP is caused by mutations in the delta-aminolevulinate dehydratase gene (ALAD) at 9q34. Being located at 9q34 means that it is on the long arm (q) of chromosome 9 in the 34 region. Of the few cases on record, the prominent symptoms are vomiting, pain in the abdomen, arms, and legs, and neuropathy. (Neuropathy refers to nerve damage that can cause pain, numbness, or paralysis.) The nerve damage associated with ADP could cause breathing impairment or lead to weakness or paralysis of the arms and legs.

Acute Intermittent Porphyria (AIP)

AIP is caused by a deficiency of porphobilinogen deaminase, which occurs due to mutations in the hydroxymethylbilane synthase gene (HMBS) located at 11q23.3. Symptoms of AIP usually do not occur unless a person with the deficiency encounters a trigger substance. Trigger substances can include hormones (for example oral contraceptives, menstruation, pregnancy), drugs, and dietary factors. Most people with this deficiency never develop symptoms.

Attacks occur after puberty and commonly feature severe abdominal pain, nausea, vomiting, and constipation. Muscle weakness and pain in the back, arms, and legs are also typical symptoms. During an attack, the urine is a deep reddish color. The central nervous system may also be involved. Possible psychological symptoms include hallucinations, confusion, seizures, and mood changes.

Congenital Erythropoietic Porphyria (CEP)

CEP is caused by a deficiency of uroporphyrinogen III cosynthase due to mutations in the uroporphyrinogen III cosynthase gene (UROS) located at 10q25.2-q26.3. Symptoms are often apparent in infancy and include reddish urine and possibly an enlarged spleen. The skin is unusually sensitive to light and blisters easily if exposed to sunlight. (Sunlight induces protoporphyrin changes in the plasma and skin. These altered protoporphyrin molecules can cause skin damage.) Increased hair growth is common. Damage from recurrent blistering and associated skin infections can be severe. In some cases facial features and fingers may be lost to recurrent damage and infection. Deposits of protoporphyrins can sometimes lead to red staining of the teeth and bones.

Porphyria Cutanea Tarda (PCT)

PCT is caused by deficient uroporphyrinogen decarboxylase. PCT is caused by mutations in the uroporphyrinogen decarboxylase gene (UROD) located at 1p34. PCT may occur as an acquired or an inherited condition. The acquired form usually does not appear until adulthood. The inherited form may appear in childhood, but often demonstrates no symptoms. Early symptoms include blistering on the hands, face, and arms following minor injuries or exposure to sunlight. Lightening or darkening of the skin may occur along with increased hair growth or loss of hair. Liver function is abnormal but the signs are mild.

Hepatoerythopoietic Porphyria (HEP)

HEP is linked to a deficiency of uroporphyrinogen decarboxylase in both the liver and the bone marrow. HEP is an autosomal recessive disease caused by mutations in the gene responsible for PCT, the uroporphyrinogen decarboxylase gene (UROD), located at 1p34. The gene is shared, but the mutations, inheritance, and specific symptoms of these two diseases are different. The symptoms of HEP resemble those of CEP.

Hereditary Coproporphyria (HCP)

HCP is similar to AIP, but the symptoms are typically milder. HCP is caused by a deficiency of coproporphyrinogen oxidase due to mutations in a gene by the same name at 3q12. The greatest difference between HCP and AIP is that people with HCP may have some skin sensitivity to sunlight. However, extensive damage to the skin is rarely seen.

Variegate Porphyria (VP)

VP is caused by a deficiency of protoporphyrinogen oxidase. There is scientific evidence that VP is caused by mutation in the gene for protoporphyrinogen oxidase located at 1q22. Like AIP, symptoms of VP occur only during attacks. Major symptoms of this type of porphyria include neurological problems and sensitivity to light. Areas of the skin that are exposed to sunlight are susceptible to burning, blistering, and scarring.

Erythropoietic Protoporphyria (EPP)

Owing to deficient ferrochelatase, the last step in the heme biosynthesis pathway—the insertion of an iron atom into a porphyrin molecule—cannot be completed. This enzyme deficiency is caused by mutations in the ferrochelatase gene (FECH) located at 18q21.3. The major symptoms of this disorder are related to sensitivity to light—including both artificial and natural light sources. Following exposure to light, a child with EPP experiences burning, itching, swelling, and reddening of the skin. Blistering and scarring may occur but are neither common nor severe. EPP is associated with increased risks for gallstones and liver complications. Symptoms can appear in childhood and tend to be more severe during the summer when exposure to sunlight is more likely.

Diagnosis

Depending on the array of symptoms a child may exhibit, the possibility of porphyria may not immediately come to a physician's mind. In the absence of a family history of porphyria, non-specific symptoms, such as abdominal pain and vomiting, may be attributed to other disorders. Neurological symptoms, including confusion and hallucinations, can lead to an initial suspicion of psychiatric disease. Diagnosis is more easily accomplished in cases in which non-specific symptoms appear in combination with symptoms more specific to porphyria, like neuropathy, sensitivity to sunlight, or certain other manifestations. Certain symptoms, such as urine the color of port wine, are hallmark signs very specific to porphyria. DNA analysis is not yet of routine diagnostic value.

A common initial test measures protoporphyrins in the urine. However, if skin sensitivity to light is a symptom, a blood plasma test is indicated. If these tests reveal abnormal levels of protoporphyrins, further tests are done to measure heme precursor levels in red blood cells and the stool. The presence and estimated quantity of porphyrin and protoporphyrins in biological samples are easily detected using spectrofluorometric testing. Spectrofluorometric testing uses a spectrofluorometer that directs light of a specific strength at a fluid sample. The porphyrins and protoporphyrins in the sample absorb the light energy and fluoresce, or glow. The spectrofluorometer detects and measures fluorescence, which indicates the amount of porphyrins and protoporphyrins in the sample.

Whether heme precursors occur in the blood, urine, or stool gives some indication of the type of porphyria, but more detailed biochemical testing is required to determine their exact identity. Making this determination yields a strong indicator of which enzyme in the heme biosynthesis pathway is defective; which, in turn, allows a diagnosis of the particular type of porphyria.

Biochemical tests rely on the color, chemical properties, and other unique features of each heme precursor. For example, a screening test for acute intermittent porphyria (AIP) is the Watson-Schwartz test. In this test, a special dye is added to a urine sample. If one of two heme precursors—porphobilinogen or urobilinogen—is present, the sample turns pink or red. Further testing is necessary to determine whether the precursor present is porphobilinogen or urobilinogen—only porphobilinogen is indicative of AIP.

Other biochemical tests rely on the fact that heme precursors become less soluble in water (able to be dissolved in water) as they progress further through the heme biosynthesis pathway. For example, to determine whether the Watson-Schwartz urine test is positive for porphobilinogen or urobilinogen, chloroform is added to the test tube. Chloroform is a water-insoluble substance. Even after vigorous mixing, the water and chloroform separate into two distinct layers. Urobilinogen is slightly insoluble in water, while porphobilinogen tends to be water-soluble. The porphobilinogen mixes more readily in water than chloroform, so if the water layer is pink (from the dye added to the urine sample), that indicates the presence of porphobilinogen, and a diagnosis of AIP is probable.

As a final test, measuring specific enzymes and their activities may be done for some types of porphyrias; however, such tests are not done as a screening method. Certain enzymes, such as porphobilinogen deaminase (the defective enzyme in AIP), can be easily extracted from red blood cells; other enzymes, however, are less readily collected or tested. Basically, an enzyme test involves adding a certain amount of the enzyme to a test tube that contains the precursor it is supposed to modify. Both the production of modified precursor and the rate at which it appears can be measured using laboratory equipment. If a modified precursor is produced, the test indicates that the enzyme is doing its job. The rate at which the modified precursor is produced can be compared to a standard to measure the efficiency of the enzyme.

Treatment

Treatment for porphyria revolves around avoiding acute attacks, limiting potential effects, and treating symptoms. Treatment options vary depending on the specific type of porphyria diagnosed. Gene therapy has been successful for both CEP and EPP. In the future, scientists expect development of gene therapy for the remaining porphyrias. Given the rarity of ALA dehydratase porphyria, definitive treatment guidelines for this rare type have not been developed.

Acute Intermittent Porphyria, Hereditary Coproporphyria, and Variegate Porphyria

Treatment for acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria follows the same basic regime. A child who has been diagnosed with one of these porphyrias can prevent most attacks by avoiding precipitating factors, such as certain drugs that have been identified as triggers for acute porphyria attacks. Individuals must maintain adequate nutrition, particularly with respect to carbohydrates. In some cases, an attack can be stopped by increasing carbohydrate consumption or by receiving carbohydrates intravenously.

When attacks occur prompt medical attention is necessary. Pain is usually severe, and narcotic analgesics are the best option for relief. Phenothiazines can be used to counter nausea, vomiting, and anxiety, and chloral hydrate or diazepam is useful for sedation or to induce sleep. Hematin, a drug administered intravenously, may be used to halt an attack. Hematin seems to work by signaling the pathway of heme biosynthesis to slow production of precursors. Older girls, who tend to develop symptoms more frequently than boys owing to hormonal fluctuations, may find ovulation-inhibiting hormone therapy to be helpful.

Gene therapy is a possible future treatment for these porphyrias. An experimental animal model of AIP has been developed and research is in progress.

Congenital Erythropoietic Porphyria

The key points of congenital erythropoietic porphyria treatment are avoiding exposure to sunlight and prevention of skin trauma or skin infection. Liberal use of sunscreens and consumption of beta-carotene supplements can provide some protection from sun-induced damage. Medical treatments such as removing the spleen or administering transfusions of red blood cells can create short-term benefits, but these treatments do not offer a cure. Remission can sometimes be achieved after treatment with oral doses of activated charcoal. Severely affected patients may be offered bone marrow transplantation which appears to confer long-term benefit.

Porphyria Cutanea Tarda

As with other porphyrias, the first line of defense is avoidance of factors, especially alcohol, that could bring about symptoms. Regular blood withdrawal is a proven therapy for pushing symptoms into remission. If an individual is anemic or cannot have blood drawn for other reasons, chloroquine therapy may be used.

Erythropoietic Protoporphyria

Avoiding sunlight, using sunscreens, and taking beta-carotene supplements are typical treatment options for erythropoietic protoporphyria. The drug cholestyramine may reduce the skin's sensitivity to sunlight as well as the accumulated heme precursors in the liver. Liver transplantation has been used in cases of liver failure, but it has not effected a long-term cure of the porphyria.

Alternative Treatment

Acute porphyria attacks can be life-threatening events, so attempts at self-treatment can be dangerous. Alternative treatments can be useful adjuncts to conventional therapy. For example, some people may find relief for the pain associated with acute intermittent porphyria, hereditary coproporphyria, or variegate porphyria through acupuncture or hypnosis. Relaxation techniques, such as yoga or meditation, may also prove helpful in pain management.

Prognosis

Even when porphyria is inherited, symptom development depends on a variety of factors. In the majority of cases, a person remains asymptomatic throughout life. About 1 percent of acute attacks can be fatal. Other symptoms may be associated with temporarily debilitating or permanently disfiguring consequences. Measures to avoid these consequences are not always successful, regardless of how diligently they are pursued. Although pregnancy has been known to trigger porphyria attacks, dangers associated with pregnancy as not as great as was once thought.

Prevention

For the most part, the porphyrias are attributable to inherited genes; such inheritance cannot be prevented. However, symptoms can be limited or prevented by avoiding factors that trigger symptom development.

Children with a family history of an acute porphyria should be screened for the disease. Even if symptoms are absent, it is useful to know about the presence of the gene to assess the risks of developing the associated porphyria. This knowledge also reveals whether a person's offspring may be at risk. Prenatal testing for certain porphyrias is possible. Prenatal diagnosis of congenital erythropoietic porphyria has been successfully accomplished. Any prenatal tests, however, would not indicate whether a child would develop porphyria symptoms; only that the potential is there.

Parental Concerns

Many children with porphyria do not have symptoms. Many acute attacks can be prevented by knowing what causes the attacks, and avoiding those things in the diet or environment that result in acute attacks.

When to Call a Doctor

Notify a doctor if the child appears to have an acute attack. Some signs and symptoms of an acute attack are: pain, red, burning or blistering skin, red urine, neurological changes, or psychological changes.

Resources

Books

Deats-O'Reilly, Diana. Porphyria: The Unknown Disease. Grand Forks, N.D.: Porphyrin Publications Press/Educational Services, 1999.

Periodicals

Gordon, Neal. "The Acute Porphyrias." Brain & Development 21 (September 1999): 373–77.

Thadani, Helen et al. "Diagnosis and Management of Porphyria." British Medical Journal 320 (June 2000): 1647–51.

Organizations

American Porphyria Foundation. PO Box 22712, Houston, TX 77227. (713) 266-9617. www.porphyriafoundation.com/.

Other

Gene Clinics. Available online at www.geneclinics.org.

National Institute of Diabetes & Digestive & Kidney Diseases. Available online at www.niddk.nih.gov.

Online Mendelian Inheritance in Man (OMIM). Available online at www3.ncbi.nlm.nih.gov/Omim.

[Article by: Mark A. Best Julia Barrett Judy C. Hawkins, MS]

Oxford Dictionary of Biochemistry:

porphyria

Top

any metabolic disorder characterized by the excretion of abnormally large amounts of various porphyrins and/or their biosynthetic precursors. Porphyrias are currently classified as primary (if inherited) or secondary (if acquired). The primary disorders fall into two broad categories: (a) the neurological/psychiatric forms and (b) the forms associated with cutaneous photosensitivity, though these two types of symptoms may in some cases overlap. The acquired disorders are much more common. There is no clear-cut association of enzyme defects with specific porphyrias. Elevated blood levels of intermediates in porphyrin biosynthesis are normally present during attacks. Elevated intermediates that are found, together with (in parentheses) associated enzymes and conditions are (1) aminolevulinic acid (or ALA) (porphobilinogen (PBG) synthase: PBG synthase deficiency porphyria; also called: ALA dehydratase: ALA dehydratase deficiency); (2) ALA and PBG (PBG deaminase; acute intermittent porphyria, variegate porphyria); (3) uroporphyrin (uroporphyrinogen decarboxylase; porphyria cutanea tarda, acute intermittent porphyria) (4) coproporphyrin (coproporphyrinogen oxidase; variegate porphyria, hereditary coproporphyria). Acquired porphyria may be due to lead exposure, some malignancies, and chronic ethanol exposure. It has been suggested that the British king, George III, suffered from a form of porphyria leading to psychiatric symptoms. See erythropoietic porphyria.

Previous:	porphyr+, porphobilinogen synthase, porphobilinogen
Next:	porphyrin, porphyrinogen, porphyrinuria

Saunders Veterinary Dictionary:

porphyria

Top

A group of inherited or acquired diseases in which there are abnormalities of porphyrin metabolism, with accumulation in the tissues and increased excretion of porphyrins.

bovine congenital erythropoietic p. — inherited as an autosomal recessive trait in cattle; from birth, affected animals have varying degrees of reddish-brown discoloration of bones, teeth and urine, anemia and photosensitization, associated with a deficiency of the enzyme uroporphyrinogen III cosynthetase.
feline p. — inherited as an autosomal dominant trait; affected cats have discolored teeth, urine and tissues, severe anemia and photosensitivity associated with a deficiency of uroporphyrinogen III cosynthetase.
inherited p. — the disease is inherited in cattle and swine and is similar to erythropoietic porphyria of humans. There are excessive amounts of porphyrins in urine and deposits in the bones and teeth causing a dark red-brown discoloration. The animals are very photosensitive and cannot live outside. See also protoporphyria, hematoporphyrinuria, osteohematochromatosis.
pig p. — an erythropoietic porphyria, similar to bovine congenital erythropoietic porphoryia, but inherited as a dominant trait. Discoloration of the teeth, bones and tissues occurs, but not of the urine, except in severely affected cases. Photosensitization is not a feature. The enzymatic defect is unknown.

Wikipedia on Answers.com:

Porphyria

Top

This article is about the medical condition. For other uses, see Porphyry (disambiguation).

Porphyria
Classification and external resources
ICD-10	E 80.0-E 80.2
ICD-9	277.1
MedlinePlus	001208
MeSH	C17.800.849.617

The porphyrias are a group of inherited or acquired disorders of certain enzymes in the heme bio-synthetic pathway (also called porphyrin pathway). They manifest with either neurological complications ("acute") or skin problems ("cutaneous"), or occasionally both. The porphyrias may be classified by the primary site of the overproduction and accumulation of the porphyrins (or their chemical precursors) as hepatic porphyrias, where porphyrins are overproduced in the liver predominantly, or erythropoietic porphyrias, where the overproduction is confined to the bone marrow and the erythrocye (red blood cell) and its precursors.

The term derives from the Greek πορφύρα, porphyra, meaning "purple pigment". The name is likely to have been a reference to the purple discolouration of feces and urine when exposed to light in patients during an attack.^[1] Although original descriptions are attributed to Hippocrates, the disease was first explained biochemically by Felix Hoppe-Seyler in 1871,^[2] and acute porphyrias were described by the Dutch physician Barend Stokvis in 1889.^[1]^[3]

The prevalence of all types of porphyria taken together has been estimated to be approximately 1 in 25,000 in the United States.^[4] The worldwide prevalence has been estimated to be somewhere between 1 in 500 to 1 in 50,000 people.^[5]

Contents

1 Signs and symptoms
- 1.1 Acute porphyrias
- 1.2 Cutaneous porphyrias
2 Diagnosis
- 2.1 Porphyrin studies
- 2.2 Additional tests
3 Pathogenesis
- 3.1 Subtypes
4 Treatment
- 4.1 Acute porphyria
- 4.2 Erythropoietic porphyrias
5 Culture and history
- 5.1 Vampires and werewolves
6 Notable cases
7 References
8 External links

Signs and symptoms

Acute porphyrias

The acute, or hepatic, porphyrias primarily affect the nervous system, resulting in abdominal pain, vomiting, acute neuropathy, muscle weakness, seizures, and mental disturbances, including hallucinations, depression, anxiety, and paranoia. Cardiac arrhythmias and tachycardia (high heart rate) may develop as the autonomic nervous system is affected. Pain can be severe and can, in some cases, be both acute and chronic in nature. Constipation is frequently present, as the nervous system of the gut is affected, but diarrhea can also occur.

Given the many presentations and the relatively low occurrence of porphyria, the patient may initially be suspected to have other, unrelated conditions. For instance, the polyneuropathy of acute porphyria may be mistaken for Guillain-Barré syndrome, and porphyria testing is commonly recommended in those situations.^[6] Systemic lupus erythematosus features photosensitivity and pain attacks and shares various other symptoms with porphyria.^[7]

Not all porphyrias are genetic, and patients with liver disease who develop porphyria as a result of liver dysfunction may exhibit other signs of their condition, such as jaundice.

Patients with acute porphyria (AIP, HCP, VP) are at increased risk over their life for hepatocellular carcinoma (primary liver cancer) and may require monitoring. Other typical risk factors for liver cancer need not be present.

Cutaneous porphyrias

The cutaneous, or erythropoietic, porphyrias primarily affect the skin, causing photosensitivity (photodermatitis), blisters, necrosis of the skin and gums, itching, and swelling, and increased hair growth on areas such as the forehead. Often there is no abdominal pain, distinguishing it from other porphyrias.

In some forms of porphyria, accumulated heme precursors excreted in the urine may cause various changes in color, after exposure to sunlight, to a dark reddish or dark brown color. Even a purple hue or red urine may be seen.

Diagnosis

Porphyrin studies

Porphyria is diagnosed through spectroscopy and biochemical analysis of blood, urine, and stool.^[8] In general, urine estimation of porphobilinogen (PBG) is the first step if acute porphyria is suspected. 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.^[9] 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.^{[citation needed]} In cases of mercury- or arsenic poisoning-induced porphyria, other changes in porphyrin profiles appear, most notably elevations of uroporphyrins I & III, coproporphyrins I & III and pre-coproporphyrin.^[10]

Repeat testing during an attack and subsequent attacks may be necessary in order to detect a porphyria, as levels may be normal or near-normal between attacks. The urine screening test has been known to fail in the initial stages of a severe life threatening attack of acute intermittent porphyria.^{[citation needed]}

The bulk (up to 90%) of the genetic carriers of the more common, dominantly inherited acute hepatic porphyrias (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria) have been noted in DNA tests to be latent for classic symptoms and may require DNA or enzyme testing. The exception to this may be latent post-puberty genetic carriers of hereditary coproporphyria.^{[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. In general, testing involves sending samples of blood, stool and urine to a reference laboratory.^[8] All samples to detect porphyrins must be handled properly. Samples should be taken during an acute attack, otherwise a false negative result may occur. Samples must be protected from light and either refrigerated or preserved.^[8]

If all the porphyrin studies are negative, one has to consider pseudoporphyria. A careful medication review often will find the inciting cause of pseudoporphyria.

Additional tests

Further diagnostic tests of affected organs may be required, such as nerve conduction studies for neuropathy or an ultrasound of the liver. Basic biochemical tests may assist in identifying liver disease, hepatocellular carcinoma, and other organ problems.

Pathogenesis

In humans, porphyrins are the main precursors of heme, an essential constituent of hemoglobin, myoglobin, catalase, peroxidase, respiratory and P450 liver cytochromes.

Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)

Deficiency in the enzymes of the porphyrin pathway leads to insufficient production of heme. Heme function plays a central role in cellular metabolism. This is not the main problem in the porphyrias; most heme synthesis enzymes—even dysfunctional enzymes—have enough residual activity to assist in heme biosynthesis. The principal problem in these deficiencies is the accumulation of porphyrins, the heme precursors, which are toxic to tissue in high concentrations. The chemical properties of these intermediates determine the location of accumulation, whether they induce photosensitivity, and whether the intermediate is excreted (in the urine or feces).

There are eight enzymes in the heme biosynthetic pathway, four of which—the first one and the last three—are in the mitochondria, while the other four are in the cytosol. Defects in any of these can lead to some form of porphyria.

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. All other porphyrias are either skin- or nerve-predominant.

Subtypes

Subtypes of porphyrias depend on what enzyme is deficient.

Enzyme	Associated porphyria	Type of porphyria	Inheritance	Symptoms	Prevalence
δ-aminolevulinate (ALA) synthase	X-linked sideroblastic anemia (XLSA)	Erythropoietic	X-linked
δ-aminolevulinate dehydratase (ALAD)	Doss porphyria/ALA dehydratase deficiency	Hepatic	Autosomal recessive ^[11]	Abdominal pain, neuropathy^[11]	Extremely rare (less than 10 cases ever reported)^[12]
hydroxymethylbilane (HMB) synthase (or PBG deaminase)	acute intermittent porphyria (AIP)	Hepatic	Autosomal dominant ^[11]	Periodic abdominal pain, peripheral neuropathy, psychiatric disorders, tachycardia^[11]	1 in 10,000^[13]-20,000^[13]
uroporphyrinogen (URO) synthase	Congenital erythropoietic porphyria (CEP)	Erythropoietic	Autosomal recessive ^[11]	Severe photosensitivity with erythema, swelling and blistering. Hemolytic anemia, splenomegaly^[11]	1 in 1,000,000 or less.^[14]
uroporphyrinogen (URO) decarboxylase	Porphyria cutanea tarda (PCT)	Hepatic	Autosomal dominant ^[11]	Photosensitivity with vesicles and bullae^[11]	1 in 10,000^[15]
coproporphyrinogen (COPRO) oxidase	Hereditary coproporphyria (HCP)	Hepatic	Autosomal dominant ^[11]	Photosensitivity, neurologic symptoms, colic^[11]	1 in 500,000^[15]
protoporphyrinogen (PROTO) oxidase	Variegate porphyria (VP)	Mixed	Autosomal dominant ^[11]	Photosensitivity, neurologic symptoms, developmental delay	1 in 300 in South Africa^[15] 1 in 75.000 in Finland^[16]
Ferrochelatase	Erythropoietic protoporphyria (EPP)	Erythropoietic	Autosomal dominant ^[11]	Photosensitivity with skin lesions. Gallstones, mild liver dysfunction^[11]	1 in 75,000^[15]-200,000^[15]
	Transient erythroporphyria of infancy			Purpuric skin lesions^[17]^:526

Treatment

Acute porphyria

Carbohydrates and heme

Often, empirical treatment is required if the diagnostic suspicion of a porphyria is high since acute attacks can be fatal. A high-carbohydrate diet is typically recommended; in severe attacks, a glucose 10% infusion is commenced, which may aid in recovery.

Hematin (trade name Panhematin) and heme arginate (trade name NormoSang) are the drugs of choice in acute porphyria, in the United States and the United Kingdom, respectively. These drugs need to be given very early in an attack to be effective; effectiveness varies amongst individuals. They are not curative drugs but can shorten attacks and reduce the intensity of an attack. Side effects are rare but can be serious. These heme-like substances theoretically inhibit ALA synthase and hence the accumulation of toxic precursors. In the United Kingdom, supplies of NormoSang are kept at two national centers; emergency supply is available from St Thomas' Hospital, London.^[18] In the United States, Lundbeck manufactures and supplies Panhematin for infusion.^[19]

Heme Arginate (NormoSang) is used during crises but also in preventive treatment to avoid crises, one treatment every 10 days

Any sign of low blood sodium (hyponatremia) or weakness should be treated with the addition of hematin or 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.^{[citation needed]}

Precipitating factors

If drugs or hormones have caused the attack, discontinuing the offending substances is essential. Infection is one of the top causes of attacks and requires immediate and vigorous treatment.

Symptom control

Pain is severe, frequently out of proportion to physical signs and often requires the use of opiates to reduce it to tolerable levels. Pain should be treated as early as medically possible, due to its severity. Nausea can be severe; it may respond to phenothiazine drugs but is sometimes intractable. Hot water baths/showers may lessen nausea temporarily, though caution should be used to avoid burns or falls.

Early identification

It is recommended that patients with a history of acute porphyria, and even genetic carriers, wear an alert bracelet or other identification at all times. 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. Some drugs are absolutely contraindicated for any patients with any porphyria.

Neurologic and psychiatric issues

Patients who experience frequent attacks can develop chronic neuropathic pain in extremities as well as chronic pain in the gut. Gut dysmotility, ileus, intussusception, hypoganglionosis, encopresis in children and intestinal pseudo-obstruction have been associated with porphyrias. This is thought to be due to axonal nerve deterioration in affected areas of the nervous system and vagal nerve dysfunction.

In these cases treatment with long-acting opioids may be indicated. Some cases of chronic pain can be difficult to manage and may require treatment using multiple modalities. Opioid dependence may develop.

Depression often accompanies the disease and is best dealt with by treating the offending symptoms and if needed the judicious use of anti-depressants. Some psychotropic drugs are porphyrinogenic, limiting the therapeutic scope.

Seizures

Seizures often accompany this disease. Most seizure medications exacerbate this condition. Treatment can be problematic: barbiturates especially must be avoided. Some benzodiazepines are safe and, when used in conjunction with newer anti-seizure medications such as gabapentin, offer a possible regime for seizure control.

Magnesium sulfate and bromides have also been used in porphyria seizures, however, development of status epilepticus in porphyria may not respond to magnesium alone. The addition of hematin or heme arginate has been used during status epilepticus.^{[citation needed]}

Underlying liver disease

Some liver diseases may cause porphyria even in the absence of genetic predisposition. These include hemochromatosis and hepatitis C. Treatment of iron overload may be required.

Hormone treatment

Hormonal fluctuations that contribute to cyclical attacks in women have been treated with oral contraceptives and luteinizing hormones to shut down menstrual cycles. However, oral contraceptives have also triggered photosensitivity and withdrawal of oral contraceptives has triggered attacks. Androgens and fertility hormones have also triggered attacks.

Erythropoietic porphyrias

These are associated with accumulation of porphyrins in erythrocytes and are rare. The rarest is Congenital erythropoetic porphyria (C.E.P) otherwise known as Gunther's disease. The signs may present from birth and include severe photosensitivity, brown teeth that fluoresce in ultraviolet light due to deposition of type one porphyrins and later hypertrichosis. Hemolytic anemia usually develops. Pharmaceutical-grade beta carotene may be used in its treatment.^[20] A bone marrow transplant has also been successful in curing CEP in a few cases, although long term results are not yet available.^[21]

The pain, burning, swelling and itching that occur in erythropoietic porphyrias generally require avoidance of bright sunlight. Most kinds of sunscreen are not effective, but SPF-rated long-sleeve shirts, hats, bandanas and gloves can help. Chloroquine may be used to increase porphyrin secretion in some EPs.^[8] Blood transfusion is occasionally used to suppress innate heme production.

Culture and history

Porphyrias have been detected in all races, multiple ethnic groups on every continent including Africans, Asians, Australian aborigines, Caucasians, Peruvian, Mexican, Native Americans, and Sami. There are high incidence reports of AIP in areas of India and Scandinavia and over 200 genetic variants of AIP, some of which are specific to families, although some strains have proven to be repeated mutations.

The links between porphyrias and mental illness have been noted for decades. In the early 1950s patients with porphyrias (occasionally referred to as "Porphyric Hemophilia"^[22]) and severe symptoms of depression or catatonia were treated with electroshock.

Vampires and werewolves

Porphyria has been suggested as an explanation for the origin of vampire and werewolf legends, based upon certain perceived similarities between the condition and the folklore.

In January 1964, L. Illis' 1963 paper, "On Porphyria and the Aetiology of Werwolves", was published in Proceedings of the Royal Society of Medicine. Later, Nancy Garden argued for a connection between porphyria and the vampire belief in her 1973 book, Vampires. In 1985, biochemist David Dolphin's paper for the American Association for the Advancement of Science, "Porphyria, Vampires, and Werewolves: The Aetiology of European Metamorphosis Legends", gained widespread media coverage, thus popularizing the connection.^[23]

The theory has since faced criticism, especially for the stigma it has placed on its sufferers. Norine Dresser's 1989 book American Vampires: Fans, Victims, Practitioners deals with this.

The theory also operates on a flawed premise, mainly in regard to a perceived harmful effect sunlight had on vampires, a property relatively late to vampire belief.^{[citation needed]} There are about eight different types of 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.^[24]

Notable cases

George III in his coronation robes

The mental illness exhibited by King George III evidenced in the regency crisis of 1788 has inspired several attempts at retrospective diagnosis. The first, written in 1855, thirty-five years after his death, concluded he suffered from acute mania. M. Guttmacher, in 1941, suggested manic-depressive psychosis as a more likely diagnosis. The first suggestion that a physical illness was the cause of King George's mental derangements came in 1966, in a paper "The Insanity of King George III: A Classic Case of Porphyria",^[25] with a follow-up in 1968, "Porphyria in the Royal Houses of Stuart, Hanover and Prussia".^[26] The papers, by a mother/son psychiatrist team, were written as though the case for porphyria had been proven, but the response demonstrated that many, including those more intimately familiar with actual manifestations of porphyria, were unconvinced. Many psychiatrists disagreed with Hunter's diagnosis, suggesting bipolar disorder as far more probable. The theory is treated in Purple Secret,^[27] which documents the ultimately unsuccessful search for genetic evidence of porphyria in the remains of royals suspected to suffer from it.^[28] In 2005 it was suggested that arsenic (which is known to be porphyrogenic) given to George III with antimony may have caused his porphyria.^[29] Despite the lack of direct evidence, the notion that George III (and other members of the royal family) suffered from porphyria has achieved such popularity that many forget that it is merely a hypothesis. In 2010 an exhaustive analysis of historical records revealed that the porphyria claim was based on spurious and selective interpretation of contemporary medical and historical sources.^[30]

Mary Stuart c.1578.

The mental illness of George III is the basis of the plot in The Madness of King George, a 1994 British film based upon the 1991 Alan Bennett play, The Madness of George III. The closing credits of the film include the comment that the illness suffered by King George has been attributed to porphyria and that it is hereditary. Among other descendants of George III theorised by the authors of Purple Secret to have suffered from porphyria (based upon analysis of their extensive and detailed medical correspondence) were his great-great-granddaughter Princess Charlotte of Prussia (Emperor William II's eldest sister) and her daughter Princess Feodora of Saxe-Meiningen. They had more success in being able to uncover reliable evidence that George III's great-great-great-grandson Prince William of Gloucester was reliably diagnosed with variegate porphyria.^{[citation needed]}

It is believed^{[by whom?]} that Mary, Queen of Scots – King George III's great-great-great-great-great-grandmother – also suffered from acute intermittent porphyria, although this is subject to much debate. It is assumed she inherited the disorder, if indeed she had it, from her father, James V of Scotland; both father and daughter endured well-documented attacks that could fall within the constellation of symptoms of porphyria.

Vlad III the Impaler was also said^{[by whom?]} to have suffered from acute porphyria, which may have started the notion that vampires were allergic to sunlight.^{[citation needed]}

Other commentators have suggested that Vincent van Gogh may have suffered from acute intermittent porphyria.^[31] It has also been imagined that King Nebuchadnezzar of Babylon suffered from some form of porphyria (cf. Daniel 4).^[32] However, the symptoms of the various porphyrias are so extensive that a wide constellation of symptoms can be attributed to one or more of them.^{[citation needed]}

Paula Frías Allende, the daughter of the Chilean novelist Isabel Allende, fell into a porphyria-induced coma in 1991,^[33] which inspired Isabel to write the autobiographical book Paula, dedicated to her.

References

^ ^a ^b Nick Lane (2002-12-16). "Born to the purple: the story of porphyria". Scientific American. http://www.sciam.com/article.cfm?articleID=000B1BEF-C051-1DF8-9733809EC588EEDF. Retrieved 2008-08-05.
^ Hoppe-Seyler F (1871). "Das Hämatin". Tubinger Med-Chem Untersuch 4: 523–33.
^ Stokvis BJ. "Over twee zeldzame kleurstoffen in urine van zieken" (in Dutch). Nederl Tijdschr Geneeskd 2: 409–417. Reprinted in Stokvis BJ (December 1989). "Over twee zeldzame kleurstoffen in urine van zieken" (in Dutch). Ned Tijdschr Geneeskd 133 (51): 2562–70. PMID 2689889.
^ eMedicine > Porphyria, Cutaneous Authors: Vikramjit S Kanwar, Thomas G DeLoughery, Richard E Frye and Darius J Adams. Updated: Jul 27, 2010
^ Genetics Home Reference > Porphyria Reviewed July 2009
^ Albers JW, Fink JK (2004). "Porphyric neuropathy". Muscle Nerve 30 (4): 410–422. doi:10.1002/mus.20137. PMID 15372536.
^ Roelandts R (2000). "The diagnosis of photosensitivity". Arch Dermatol 136 (9): 1152–1157. doi:10.1001/archderm.136.9.1152. PMID 10987875.
^ ^a ^b ^c ^d Thadani H, Deacon A, Peters T (2000). "Diagnosis and management of porphyria". BMJ 320 (7250): 1647–1651. doi:10.1136/bmj.320.7250.1647. PMC 1127427. PMID 10856069. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1127427.
^ Anderson KE, Bloomer JR, Bonkovsky HL et al (2005). "Recommendations for the diagnosis and treatment of the acute porphyrias". Ann. Intern. Med. 142 (6): 439–50. PMID 15767622.
^ Woods, J.S. (1995). "Porphyrin metabolism as indicator of metal exposure and toxicity". In Goyer, R.A. & Cherian, M.G.. Toxicology of metals, biochemical aspects. 115. Berlin: Springer. pp. 19–52, Chapter 2.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m Table 18-1 in: Marks, Dawn B.; Swanson, Todd; Sandra I Kim; Marc Glucksman (2007). Biochemistry and molecular biology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 0-7817-8624-X.
^ Overview of the Porphyrias at The Porphyrias Consortium (a part of NIH Rare Diseases Clinical Research Network (RDCRN)) Retrieved June 2011
^ ^a ^b Medscape > Diseases of Tetrapyrrole Metabolism - Refsum Disease and the Hepatic Porphyrias Author: Norman C Reynolds. Chief Editor: Stephen A Berman. Updated: Mar 23, 2009
^ Thadani, H.; Deacon, A.; Peters, T. (2000). "Diagnosis and management of porphyria". BMJ 320 (7250): 1647–1651. doi:10.1136/bmj.320.7250.1647. PMC 1127427. PMID 10856069. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1127427. edit
^ ^a ^b ^c ^d ^e Arceci, Robert.; Hann, Ian M.; Smith, Owen P. (2006). Pediatric hematolog. Malden, Mass.: Blackwell Pub.. ISBN 978-1-4051-3400-2.
^ Mustajoki, P. (1980). "Variegate porphyria. Twelve years' experience in Finland". The Quarterly journal of medicine 49 (194): 191–203. PMID 7433635. edit
^ James, William D.; Berger, Timothy G. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
^ "9.8.2: Acute porphyrias". British National Formulary (BNF 57). United Kingdom: BMJ Group and RPS Publishing. March 2009. p. 549. ISBN 9780853698456.
^ American Porphyria Foundation (2010). "Panhematin for Acute Porphyria". http://www.porphyriafoundation.com/testing-and-treatment/medications-for-porphyria/panhematin. Retrieved 2010-08-05.
^ Martin A Crook.2006. Clinical chemistry and Metabolic Medicine. seventh edition. Hodder Arnold. ISBN 0-340-90616-2
^ Faraci M, Morreale G, Boeri E et al (2008). "Unrelated HSCT in an adolescent affected by congenital erythropoietic porphyria". Pediatr Transplant 12 (1): 117–120. doi:10.1111/j.1399-3046.2007.00842.x. PMID 18186900.
^ Denver, Joness. "An Encyclopaedia of Obscure Medicine". Published by University Books, Inc., 1959.
^ One example is the comic book Ultimate Comics Avengers 3 #1 (October 2010), in which writer Mark Millar employed porphyria as the explanation for vampires in that fictional universe.
^ Puy H, Gouya L, Deybach JC (March 2010). "Porphyrias". Lancet 375 (9718): 924–37. doi:10.1016/S0140-6736(09)61925-5. PMID 20226990.
^ Macalpine I, Hunter R (January 1966). "The "insanity" of King George 3d: a classic case of porphyria". Br Med J 1 (5479): 65–71. doi:10.1136/bmj.1.5479.65. PMC 1843211. PMID 5323262. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1843211.
^ Macalpine I, Hunter R, Rimington C (January 1968). "Porphyria in the royal houses of Stuart, Hanover, and Prussia. A follow-up study of George 3d's illness". Br Med J 1 (5583): 7–18. doi:10.1136/bmj.1.5583.7. PMC 1984936. PMID 4866084. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1984936.
^ Warren, Martin; Rh̲l, John C. G.; Hunt, David C. (1998). Purple secret: genes, "madness" and the Royal houses of Europe. London: Bantam. ISBN 0-593-04148-8.
^ The authors demonstrated a single point mutation in the PPOX gene, but not one which has been associated with disease.
^ Cox TM, Jack N, Lofthouse S, Watling J, Haines J, Warren MJ (2005). "King George III and porphyria: an elemental hypothesis and investigation". Lancet 366 (9482): 332–335. doi:10.1016/S0140-6736(05)66991-7. PMID 16039338.
^ Peters TJ, Wilkinson D (2010). "King George III and porphyria: a clinical re-examination of the historical evidence". History of Psychiatry 21: 3–19. doi:10.1177/0957154X09102616.
^ Loftus LS, Arnold WN (1991). "Vincent van Gogh's illness: acute intermittent porphyria?". BMJ 303 (6817): 1589–1591. doi:10.1136/bmj.303.6817.1589. PMC 1676250. PMID 1773180. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1676250.
^ Beveridge A (2003). "The madness of politics". J R Soc Med 96 (12): 602–604. doi:10.1258/jrsm.96.12.602. PMC 539664. PMID 14645615. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=539664.
^ Allende, Isabel (1995). Paula. New York, NY: HarperCollins Publishers. ISBN 0060172533.

External links

Heme metabolism disorders (E80, 277.1, 277.4)

Porphyria,
hepatic and erythropoietic
(porphyrin)

early mitochondrial: ALAD porphyria · Acute intermittent porphyria

cytoplasmic: Gunther disease/congenital erythropoietic porphyria · Porphyria cutanea tarda/Hepatoerythropoietic porphyria

late mitochondrial: Hereditary coproporphyria · Variegate porphyria · Erythropoietic protoporphyria

Hereditary hyperbilirubinemia
(bilirubin)

unconjugated: Gilbert's syndrome · Crigler-Najjar syndrome · Lucey-Driscoll syndrome

conjugated: Dubin–Johnson syndrome · Rotor syndrome

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

M: MYL

cell/phys (coag, heme, immu, gran), csfs

rbmg/mogr/tumr/hist, sysi/epon, btst

drug (B1/2/3+5+6), btst, trns

This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)

Donate to Wikimedia

		American Heritage Dictionary. The American Heritage® Dictionary of the English Language, Fourth Edition Copyright © 2007, 2000 by Houghton Mifflin Company. Updated in 2009. Published by Houghton Mifflin Company. All rights reserved. Read more
		Word Overheard by Answers.com. © 1999-present by Answers Corporation. All rights reserved. Read more
		Gale Encyclopedia of Children's Health. © 2006 by The Gale Group, Inc. All rights reserved. Read more
		Oxford Dictionary of Biochemistry. Oxford University Press. Oxford Dictionary of Biochemistry and Molecular Biology © 1997, 2000, 2006 All rights reserved. Read more
		Saunders Veterinary Dictionary. Saunders Comprehensive Veterinary Dictionary 3rd Edition. Copyright © 2007 by D.C. Blood, V.P. Studdert and C.C. Gay, Elsevier. All rights reserved. Read more
		Wikipedia on Answers.com. This article is licensed under the Creative Commons Attribution/Share-Alike License. It uses material from the Wikipedia article Porphyria. Read more

	What are the effects of porphyria? Read answer...
	What is a description of porphyrias? Read answer...
	What is an acute porphyria? Read answer...

	Who studied porphyria?
	What are the signs of porphyria?
	How did porphyria die?