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About Porphyrias

About the Porphyria's.  Have you looked to see all the types there are?  Which one have you been diagnosed with?  What type of therapy or treatment is available for you?  Many of you are new to Porphyria and are trying to get a proper diagnosis.  This information comes directly from the APF.  If you need help in getting a diagnosis or have a questions on the different types please give the APF a call 1.866.APF.3635. www.porphyriafoundation.org

About Porphyria

Porphyria is not a single disease but a group of eight inherited genetic disorders that differ considerably from each other. A common feature in all Porphyrias is the accumulation in the body of porphyrins or porphyrin precursors. Although these are normal body chemicals, they normally do not accumulate. Precisely which of these chemicals builds up depends on the type of Porphyria.
The terms porphyrin and porphyria are derived from the Greek word porphyrus, meaning purple. Urine from some Porphyria patients may be reddish-purple in color due to the presence of excess porphyrins and related substances in the urine, and the urine may darken after exposure to light.

Cause

Porphyria arises as a result of a malfunction in one of the eight steps in the body's synthesis of a complex molecule called heme. Heme is essential for the transport of oxygen to cells in the body. If any step in the synthesis of heme is blocked, an intermediate chemical accumulates in the cell, resulting in oxygen depletion. Those intermediate chemicals, known as porphyrins or porphyrin precursors, are the substances of which heme is composed. Each type of Porphyria represents a deficiency of a specific enzyme needed for the synthesis of heme.

Types of Porphyria

Most commonly the Porphyrias are divided into the “acute” and “cutaneous” Porphyrias, depending on the primary symptoms.  For many with one of the four acute Porphyrias, Porphyria attacks generally evolve and become more severe over several days, especially the abdominal pain; two of these, Variegate Porphyria and Hereditary Coproporphyria, may also have skin symptoms of blistering after sun exposure. The cutaneous Porphyrias present with blistering and scarring of the skin, pain, and/or redness and swelling in sun-exposed areas.

The Acute Porphyrias

There are four types of acute Porphyrias: Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), and δ-aminolevulinic acid dehydratase (ALAD) Porphyria (ADP), which are characterized by episodes of debilitating attacks. These are genetic disorders that are very rare and may be difficult to diagnose for this reason. It is estimated that about 1 in 10,000 Europeans or people of European ancestry have a mutation in one of the genes that cause AIP, VP or HCP. These mutations have been found in all races and many other ethnicities in addition to Europeans.
Approximately 80-90% of individuals who carry a gene mutation for Acute Intermittent Porphyria, Variegate Porphyria, and Hereditary Coproporphyria remain asymptomatic, and others may have only one or a few acute attacks throughout life. The most frequent symptom is severe abdominal pain and is often accompanied by nausea, vomiting, and constipation. Other symptoms may include heart palpitations, seizures, and hallucinations. People with VP and HCP may also have skin symptoms of blistering after sun exposure.

The Cutaneous Porphyrias

All but one of the cutaneous Porphyrias cause skin blistering and fragility on sun-exposed areas of the body, most commonly the backs of the hands, forearms, face, ears and neck. The cutaneous Porphyrias are: Porphyria Cutanea Tarda (PCT), Hepatoerythropoietic Porphyria (HEP), Congenital Erythropoietic Porphyria (CEP), Erythropoietic Protoporphyria (EPP), and X-linked Protoporphyria (XLP). CEP and HEP occur in childhood with severe blistering skin lesions. PCT occurs in adulthood generally and has less severe blistering skin lesions after sun exposure. Erythropoietic Protoporphyria (EPP) and X-linked Protoporphyria (XLP) have the same symptoms of painful, but non-blistering, reactions to sunlight. There can also be swelling and redness of the sun exposed areas of the skin with EPP and XLP.

Prevalence

The Porphyrias are rare diseases. Taken together, all forms of Porphyria afflict fewer than 200,000 people in the United States. Based on European studies, the prevalence of the most common Porphyria, Porphyria Cutanea Tarda (PCT), is 1 in 10,000; the most common acute Porphyria, Acute Intermittent Porphyria (AlP), is about 1 in 20,000; and the most common erythropoietic Porphyria, Erythropoietic Protoporphyria (EPP), is estimated at 1 in 50,000 to 75,000. Congenital Erythropoietic Porphyria (CEP) is extremely rare with prevalence estimates of 1 in 1,000,000 or less. Only 9 cases of ALAD-deficiency Porphyria (ADP) are documented.

Signs and Symptoms

The signs and symptoms and vary significantly from one type of Porphyria to the next. Because the symptoms of the various Porphyrias may resemble symptoms of other more common disorders, diagnosis may be difficult. The onset, severity and type of symptoms can vary greatly in individuals with a specific type of Porphyria. This variation may depend on, in part, the amount of residual enzyme activity in each individual. Individuals with more significant enzyme deficiency may have more severe symptoms and earlier onset. Individuals with partial deficiency will have milder symptoms, and some individuals will not develop any symptoms (asymptomatic). It is important to note that affected individuals may not have all of the symptoms discussed below. Affected individuals should talk to their medical team about their specific case, associated symptoms and overall prognosis.

Acute Intermittent Porphyria

Abdominal pain is the most common complaint in Acute Intermittent Porphyria (AIP). In addition, some of the following symptoms occur with varying frequency: pain in the arms and leg, generalized weakness, vomiting, confusion, constipation, tachycardia, fluctuating blood pressure, urinary retention, psychosis, hallucinations, and seizures. The muscle weakness may progress to respiratory paralysis, necessitating artificial respiration. Porphobilinogen (PBG) and Aminolevulenic Acid (ALA), porphyrin precursors, are elevated during the attack but may be consistently high in some patients. Urine may exhibit a purple-red color. Unlike other forms of Porphyria, sun sensitivity is not present in this type.

Variegate Porphyria

Variegate Porphyria (VP) is characterized by abrasions, blisters, and erosions of the skin which are commonly seen during the second and third decade. These lesions tend to heal slowly, often leaving pigmented or slightly depressed scars. The patients experience sensitivity to light and fragility of skin exposed to the sun. Although in many patients’ manifestations remain limited to the skin, episodes similar to those of acute Porphyria are not uncommon. Therefore, the symptoms, drugs, precautionary measures, and treatment described for Acute Intermittent Porphyria are applicable to Variegate Porphyria.

Hereditary Coproporphyria

The large amounts of coproporphyrin present in Hereditary Coproporphyria (HCP) makes the patient sensitive to sunlight, but skin disease is rarely severe in this type of Porphyria. Clinically it resembles Variegate Porphyria except that a larger percentage of affected individuals exhibit few symptoms. Other symptoms are similar to those listed for Acute Intermittent Porphyria.

Erythropoietic Protoporphyria

Erythropoietic Protoporphyria (EPP) can have mild to severe light sensitivity and burning on exposure to the sunlight. Usually, the symptoms subside in twelve to twenty-four hours and heal without significant scarring or discoloration to the skin. The skin lesions may also progress to a chronic stage persisting for weeks and healing with a superficial scar. These manifestations generally begin in childhood. They are more severe in the summer and can recur throughout life. Affected skin, at times, exhibits the fragility or blister formation seen in other photosensitizing types of Porphyria. Liver dysfunction along with gallbladder, bile duct or bile involvement (hepatobiliary system) may be associated with significant liver damage.

Porphyria Cutanea Tarda

In Porphyria Cutanea Tarda (PCT), exposed skin shows abnormalities similar to those found in Variegate Porphyria. They range from slight fragility of the skin to persistent scarring and disfiguration. Due to fragility of the skin, minor trauma may induce blister formation. Areas of increased and decreased pigment content may be noted on the skin. Blistering of light exposed skin and increased hair growth, especially on the face, are also characteristic.

Congenital Erythropoietic Porphyria

Congenital Erythropoietic Porphyria (CEP) is a very rare disease with approximately 150 patients reported in the world. CEP is often manifested shortly after birth with dark urine and sunlight sensitivity causing blistering and skin fragility. Later, brownish, fluorescent teeth, increased hair growth, and pronounced scarring may occur. In some cases, loss of fingers and toes and cartilage from ears or nose may be noted.

ALA-D Porphyria

ALA-D Porphyria (ADP) symptoms usually arise from effects on the nervous system and/or the skin. Sometimes, the cause of the nervous system symptoms is not clear. Skin manifestations include burning, blistering, and scarring of the sun exposed areas. The disease usually manifests after puberty, and more commonly occurs in women. The most common symptom is severe abdominal pain. Other characteristics are nausea, vomiting, rapid heart rate, increased blood pressure, confusion and/or seizures, and the passing of ALA (delta-aminolevulinic acid) in the urine.

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