APEX
American Porphyrias
Expert Collaborative
APEX advances fundamental, translational, and clinical research in the porphyrias and heme biosynthesis, while actively promoting awareness and knowledge among physicians, researchers, and scientists. Through national coordination and global collaboration with expert porphyria groups, APEX ensures the highest standards of care and fosters innovation in the field.
Our Programs
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The Porphyrias Consortium
The Porphyrias Consortium is a nationwide network of 14 specialized Porphyria Centers of Expertise across the United States.
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Western Hemisphere Network
The Western Hemisphere network unites healthcare providers across North, Central, and South America, who care for patients with porphyria.
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International Porphyrias Symposium
The International Porphyrias Symposium is a biennial gathering dedicated to advancing knowledge in heme biosynthesis and the pathogenesis and treatment of the porphyrias.
About Porphyria
Porphyrias are a group of mostly inherited disorders caused by mutations in genes that help the body make heme – a molecule needed for carrying oxygen in the blood and for other vital functions. Each type of porphyria is caused by a defect in a specific enzyme in the heme production pathway, leading to the buildup of different heme precursors. This is why the different types of porphyrias have different symptoms.
The porphyrias can be grouped into two main categories based on their primary symptoms:
Acute Hepatic Porphyrias (AHP)
Acute porphyrias cause episodes of severe abdominal pain, known as attacks, which can last for several days. Other symptoms may also occur during these attacks. Triggers for attacks include certain medications, fasting, hormonal changes, infections, or stress. Some people with acute porphyrias may also develop long-term health issues, such as chronic pain and kidney disease. Most acute porphyrias do not affect the skin, but hereditary coproporphyria and variegate porphyria can sometimes cause blistering of the skin after sun exposure.
Most people who have a gene mutation that can cause acute intermittent porphyria, variegate porphyria, or hereditary coproporphyria never have symptoms. About 80-90% of these individuals remain healthy. Others may have a few attacks of abdominal pain or other symptoms in their lifetime. A small number suffer from recurrent attacks.
Types of acute hepatic porphyria:
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AIP is an inherited disorder characterized by potentially life-threatening acute attacks. These attacks can be triggered by certain medications, fasting, hormonal changes, infections, or stress. The main symptom of an attack is severe abdominal pain. Other symptoms can include confusion, constipation, hallucinations, nausea, restlessness, seizures, sensory changes, vomiting, and weakness. AIP is caused by mutations in the HMBS gene, which produces one of the enzymes in the heme production pathway. Without enough of this enzyme, chemicals called ALA and PBG build up, leading to symptoms. Most people with mutations in the HMBS gene never develop acute attacks. People with AIP also have an increased risk of developing chronic kidney disease and liver cancer.
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A rare, inherited, metabolic disorder characterized by deficiency of the enzyme coproporphyrinogen oxidase, which allows for build-up of porphyrin precursors. Porphyrins are substances that bind metals to form complexes, such as the iron found in red blood cells. Symptoms are triggered by drug and alcohol abuse, infections, hormonal changes, and dietary changes. Symptoms include mild to severe abdominal pain, back and extremity pain, vomiting, constipation, rapid or irregular heartbeats, high blood pressure, orthostasis (sudden drop in blood pressure with positional changes), seizures, hyponatremia (low blood sodium levels), skin lesions, psychological symptoms, and peripheral neuropathy (sensory changes and profound muscle weakness in the extremities).
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A rare, metabolic disorder characterized by deficiency of the enzyme protoporphyrinogen oxidase (PPO), which allows for build-up of porphyrins and porphyrin precursors. Porphyrins are substances that bind metals to form complexes, such as the iron found in red blood cells. Symptoms include abdominal and extremity pain, nausea, vomiting, constipation, bladder dysfunction, convulsions, profound muscle weakness, tachycardia (rapid heartbeat), hypertension (high blood pressure), and cutaneous photosensitivity (skin hyperreactivity to light) resulting in blistering skin lesions, hypertrichosis (excessive hair growth), and discoloration. Risk for developing chronic kidney disease and hepatocellular carcinoma (liver cancer) increases.
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A rare, inherited, metabolic disorder characterized by complete deficiency of the enzyme delta-aminolevulinic acid (ALA) dehydratase, which allows for build-up of the porphyrin precursor, ALA. Porphyrins are substances that bind metals to form complexes, such as the iron found in red blood cells. Symptoms during acute attacks include severe abdominal pain, vomiting, constipation, growth and feeding problems in infancy, ataxia (lack of coordination), psychological changes, seizures, hypertension (high blood pressure), tachycardia (rapid heartbeat), difficulty breathing, and peripheral neuropathy (sensory changes and profound muscle weakness in the extremities).
Cutaneous Porphyrias
Cutaneous porphyrias primarily affect the skin after sun-exposure. People with these disorders experience photosensitivity, meaning their skin reacts to sunlight on exposed areas like the hands and face. There are two main patterns of skin symptoms that different types of cutaneous porphyrias are characterized by:
Blistering and fragile skin. This is seen in porphyria cutaneous tarda, hepatoerythropoietic porphyria, and congenital erythropoietic porphyria. These skin symptoms look the same as the skin symptoms in two of the acute porphyrias, hereditary coproporphyria and variegate porphyria.
Pain, burning, tingling, and swelling. This is seen in erythropoietic protoporphyria and X-linked protoporphyria.
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Congenital erythropoietic porphyria (CEP), also known as Gunther disease, is a very rare form of porphyria. The major symptoms are sensitivity of the skin to sunlight and some types of artificial light, and anemia, which can be very severe.
Sunlight exposure causes blistering. The fluid-filled blisters rupture and get infected. These infected wound can lead to scarring, bone loss, and deformities. The hands, arms, and face are the most commonly affected areas. Increased hair growth (hypertrichosis) on sun-exposed skin, brownish-colored teeth (erythrodontia), and reddish-colored urine are common. There may be bone fragility and vitamin deficiencies, especially vitamin D. The spleen can be enlarged, particularly in people with anemia.
The severity and onset of symptoms can vary. For many, the onset of symptoms and diagnosis are often in infancy. Some do not develop symptoms until adulthood, their symptoms are usually milder and primarily skin related.
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Erythropoietic protoporphyria (EPP) and x-linked protoporphyria (XLP), collectively know as the protoporphyrias, are characterized by severe pain in the skin with exposure to sunlight and some forms of artificial light.
People with protoporphyria first experience tingling, itching, or burning which is like a warning sign to avoid further sun exposure. With ongoing exposure, the symptoms progress to severe pain that may be followed by swelling or redness. The most common areas affected include the back of the hands and the face.
The amount of sunlight tolerance varies between people with some able to tolerate only a few minutes and others who can stay out in the sun for much longer.
Symptoms typically appear in childhood. EPP is equally common in males and females.
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Hepatoerythropoietic porphyria (HEP) is a very rare form of porphyria. The major symptoms are sensitivity of the skin to sunlight and some types of artificial light.
Light exposure causes blistering. The fluid-filled blisters rupture and get infected. These wound infected can lead to scarring, bone loss, and deformities. The hands, arms, and face are the most commonly affected areas. Increased hair growth (hypertrichosis) on sun-exposed skin and reddish-colored urine are common.
Symptoms usually start in infancy or early childhood.
HEP is a much more severe form of porphyria cutanea tarda (PCT), as in HEP both copies of the UROD gene are affected. The parents of someone with HEP will both have familial PCT, though they may not have any symptoms.
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Porphyria cutanea tarda (PCT) is the most common form of porphyria in the United States.
PCT symptoms usually start in adulthood. Sun-exposed areas of the skin, most commonly face, hands and feet, develop blisters. Skin may also become fragile, darkened or thicken, people with PCT may have increased hair growth.
PCT is the only form of porphyria that does not always have underlying genetic mutation. Risk factors for developing PCT include excessive alcohol use, smoking, use of oral estrogens (such as birth control pills or hormone replacement therapy), hepatitis C infection, HIV infection, and a disease called hemochromatosis, which causes iron overload.
About 80% of PCT patients have Sporadic PCT where there is no known gene changes. The remaining 20% have genetic change affecting one copy of the UROD gene, which is called Familial PCT, other risk factors are usually also present in this type of PCT.
The blisters and other skin symptoms of PCT look very similar to two forms of acute hepatic porphyria (variegate porphyria and hereditary coproporphyria), however the acute attacks that are seen in the acute porphyrias do NOT occur in PCT. Biochemical testing is required to confirm the porphyria type. Confirmation is important because the treatment and management of PCT is different from the treatment of the acute hepatic porphyrias.
Each type of porphyria is caused by a mutation in the gene coding for a specific enzyme in the heme production pathway. Porphyria cutaneous tarda (PCT) is different from other types of porphyria. Most people with PCT do not have a gene mutation. Instead, they develop the condition due to other factors, meaning it is mostly acquired rather than inherited.
Types of porphyria, their patterns of inheritance, and the enzyme that is deficient in each.
Each type of porphyria is caused by a mutation in the gene coding for a specific enzyme in the heme production pathway. Porphyria cutaneous tarda (PCT) is different from other types of porphyria. Most people with PCT do not have a gene mutation. Instead, they develop the condition due to other factors, meaning it is mostly acquired rather than inherited.
The inherited porphyrias are either autosomal dominant (inherited from one parent), autosomal recessive (inherited from both parents), or X-linked (the gene is located on the X-chromosome). "Autosomal" genes always occur in pairs, with one coming from each parent. Individuals with an autosomal dominant form of porphyria have one mutated gene paired with a normal gene, and there is a 50% chance with each pregnancy that the mutated gene will be passed to a child.
Individuals with an autosomal recessive type of porphyria have mutations on both copies of a specific gene, one passed to them from each of their parents. Each of their children will inherit one mutated gene for that porphyria, and the child will be a “carrier” but will not have symptoms.
In X-linked disorders, the gene is located on one of the sex chromosomes, called the X-chromosome. Females have two X-chromosomes, and males have one X-chromosome and one Y-chromosome. Both males and females will likely have symptoms from a mutated gene on the X-chromosome, but females, with a normal gene on the other X-chromosome, usually are less severely affected than males. The risk for children depends on the gender of the affected parent. A female with an X-linked gene mutation will have a 50% risk of passing that mutation to any of her children with each pregnancy. However, a male will pass the mutation to all of his daughters but none of his sons.
There are many laboratory tests available for the porphyrias, and the right tests to order depend on the type of porphyria the doctor suspects. When abdominal and neurological symptoms suggest an acute porphyria, the best screening tests are urinary aminolevulinic acid (ALA) and porphobilinogen (PBG). When there are cutaneous symptoms that suggest porphyria, the best screening test is a plasma porphyrin assay. If one of these screening tests is abnormal, more extensive testing, including urinary, fecal, and red blood cell porphyrins, are often indicated.
DNA testing to identify the specific mutation in an individual’s porphyria-causing gene is also recommended. Before requesting DNA testing, it is helpful that patients have biochemical testing. However, many patients have not had an acute attack or are not symptomatic at present, so biochemical testing may be inconclusive.
In contrast, DNA testing is the most accurate and reliable method for determining if a person has a specific porphyria and is considered the "gold standard" for the diagnosis of genetic disorders. If a mutation (or change) in the DNA sequence is found in a specific Porphyria-causing gene, the diagnosis of that Porphyria is confirmed. DNA analysis will detect more than 97% of disease-causing mutations. DNA testing can be performed whether the patient is symptomatic or not. Once a mutation has been identified, DNA analysis can then be performed on other family members to determine if they have inherited that Porphyria, thus allowing identification of individuals who can be counseled about appropriate management in order to avoid or minimize disease complications.
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