Porphyria

Porphyria is a group of metabolic disorders associated with impaired red blood pigment production. Learn more!

Porphyria

The porphyria is a group of rare metabolic diseases associated with impaired formation of the red blood pigment heme. Typical porphyria symptoms include colicky abdominal pain and intense photosensitivity of the skin. Most of the porphyrias are hereditary and therefore treatable only symptomatically. Find out more about porphyria here.

ICD codes for this disease: ICD codes are internationally valid medical diagnosis codes. They are found e.g. in doctor's letters or on incapacity certificates. E80

Product Overview

porphyria

  • description

  • symptoms

  • Causes and risk factors

  • Examinations and diagnosis

  • treatment

  • Disease course and prognosis

Porphyria: description

Porphyries are rare and little known. They form a group of related metabolic diseases and express themselves mainly on the skin and nervous system.

Metabolism is the sum of all the biochemical processes in the body that involve the buildup, removal and rebuilding of substances. Enzymes are involved in these processes, each of which handles one step in the reaction chain. Many different metabolic pathways take place in the human body - one of them is the build-up of heme, which the body needs, among other things, for the red blood cells. The heme consists of a so-called porphyrin - an organic-chemical compound, of which there are different in nature - with an iron ion in the middle.

In the metabolic disorder porphyria heme can not be formed regularly because of an enzyme defect. The result is that the heme precursors build up because they can not be further processed. These precursors are also porphyrins - hence the name of the disease.

Why is porphyrin heme important?

Heme is an important component of hemoglobin - the red blood pigment in the red blood cells, which is responsible for the transport of oxygen in the blood: hemoglobin is composed of a protein complex with a central heme group. The iron ion from heme can bind molecular oxygen.

Heme is also part of the red muscle pigment myoglobin and the cytochrome. These are enzymes that are of crucial importance in the breakdown of pharmaceuticals.

Forms of porphyria

There are seven different porphyria forms - four acute and three non-acute variants.

The four acute porphyria forms are:

  • the acute intermittent porphyria,
  • the porphyria variegata,
  • hereditary coproporphyria and
  • the very rare Doss porphyria.

They are called acute because they suddenly cause abdominal pain that can last for several days. In the case of Porphyria variegata and hereditary coproporphyria, sufferers additionally suffer from photosensitivity of the skin.

The three non-acute porphyria species on the other hand show no acute abdominal pain and mainly affect the skin. They include:

  • the porphyria cutanea tarda,
  • the erythropoietic protoporphyria and
  • the rare congenital erythropoietic porphyria (Günther's disease).

Heme formation mainly occurs in the bone marrow, to a lesser extent in the liver. Therefore, the seven forms of porphyria can also be divided into two groups, depending on the location where the heme precursors mainly accumulate due to an enzyme defect. Accordingly, one distinguishes:

  • erythropoietic porphyria (Bone marrow): erythropoietic protoporphyria, congenital erythropoietic porphyria (Günther's disease)
  • hepatic porphyrias (Liver): Acute intermittent porphyria, Porphyria variegata, Hereditary coproporphyria, Doss porphyria, Porphyria cutanea tarda

Porphyria: frequency

Only two forms, porphyria cutanea tarda and acute intermittent porphyria, are found in significant numbers during adulthood. Erythropoietic protoporphyria is the most common childhood porphyria form. All other forms are very rare.

Porphyria: symptoms

Depending on where the enzyme defect is present, different porphyria symptoms manifest. The signs of the three most common porphyria forms are:

Acute intermittent porphyria (AIP)

Acute intermittent porphyria is characterized by a variety of symptoms, which makes it difficult for the doctor to make the right diagnosis. The severity of this form of porphyria varies greatly: while 90 percent of cases are asymptomatic (ie without discomfort), there are also recurrent cases of paralysis, which, if the respiratory muscles are affected, can lead to death.

The disease mainly causes acute abdominal pain as well as neurological and psychiatric symptoms. These occur - as the term intermittently suggests - often shuddering. Most medications, hormonal changes (such as pregnancy, menstruation) or carbohydrate deficiency caused by diets or fasting such acute relapses.An acute episode usually only lasts for one to two weeks, but may persist much longer if symptoms of paralysis occur.

This is what an acute boost looks like:

  • Violent colicky abdominal pain, most of which is localized in the lower abdomen, signaling the onset of a seizure.
  • fever
  • Vomiting and chronic constipation, which is difficult to treat.
  • Reddish urine, which darkens after some time (dark spots in the underwear!)
  • Neurological symptoms such as incomplete (paresis) or complete paralysis (paralysis), muscle weakness and sensory disorders (ie disorders in the area of ​​vision, hearing, taste, smell and sense of balance)
  • Mental mood swings, delusions, coma and states of confusion (delirium)
  • Cardiovascular problems such as palpitations (tachycardia) and high blood pressure (hypertension)

Porphyria cutanea tarda

In Porphyria cutanea tarda, the heme precursors (porphyrins) accumulate in the liver, enter the blood and enter the skin. The result is a strong photosensitivity: The UV rays in sunlight form skin blisters on the unprotected skin areas such as hands, face and neck. In addition, since the skin is very vulnerable, such liquid-filled bubbles can form even with the smallest injuries and everyday work. The blisters burst and heal with the formation of bright, raised scars. Otherwise, the skin is stained brown by embedded porphyrins.

Those affected may also be overly hairy on the forehead, cheeks and around the eyes (hypertrichosis).

Patients also often suffer from liver disease (such as fatty liver or cirrhosis). The urine of the patients may be brown-red.

Erythropoietic Protoporphyria (EPP)

The skin is extremely sensitive to light: the porphyrin, which can not be further built up to heme due to the enzyme defect, circulates in the blood. Under the action of sunlight, it forms oxygen radicals in the skin that cause burn-like appearance of the skin with itching and pain. Just a few minutes of sunlight can trigger the skin symptoms. Even indirect light such as reflective surfaces can cause discomfort. The damaged skin can regenerate completely, but this can take hours to days. Glycoproteins can accumulate on the mostly unprotected areas of the skin, such as the nose or hands, causing the skin to thicken and coarsen.

In addition, some sufferers suffer from impaired liver function, which in ten percent of cases, develops into a chronic disease of the liver, cirrhosis of the liver.

Porphyria: causes and risk factors

The heme formation takes place via eight different reaction steps. Each step is made possible by a specific enzyme, seven of the eight enzymes may be defective - porphyria is present.

The intermediates (heme precursors) formed in the reaction chain before the defective enzyme can not be processed further and accumulate. However, most of the production pathway of the heme is only partially blocked and is compensated by regulatory mechanisms, so that the heme formation at least partially works. Nevertheless, heme precursors (porphyrins) accumulate, which can cause various symptoms - usually in the form of porphyria attacks, triggered by certain factors such as infections or the intake of medication.

Why porphyrins make you sick?

The heme precursors, which can not be processed, deposit in the organs, especially in the skin and liver. In addition, the porphyrins are usually excreted in an increased amount with the stool and urine. A red or orange urine is therefore a typical symptom of some porphyria forms.

The accumulation of heme precursors in acute porphyrias mainly causes discomfort in the abdominal area and nervous system. In non-acute porphyria, on the other hand, skin changes are in the foreground.

Genetic change as a cause of porphyria

In porphyria, the genetic material (gene) of the defective enzyme is altered by a mutation. This mutation is inherited in most cases, generally autosomal dominant, that is independent of the sex chromosomes. Porphyria is usually only expressed together with external influences such as alcohol consumption, certain medications or infections.

In some cases, porphyria is acquired through poisoning (such as lead poisoning).

Acute intermittent porphyria (AIP)

Acute intermittent porphyria is the most common acute porphyria. Women are affected three times more often than men. As a rule, this porphyria form is not noticed until the age of 20 to 40.

In acute intermittent porphyria, the third enzyme in the heme production pathway, porphobilinogen deaminase, is defective. This defect is inherited autosomal dominant. However, complaints usually only appear when factors such as certain medications, alcohol or infections are added. These then trigger an acute disease impulse ("intermittent" means, occurring intermittently).

Porphyria cutanea tarda

Porphyria cutanea tarda is generally the most common form of porphyria and is also inherited as an autosomal dominant. It can be heterozygous (genetic defect on one of the two paired chromosomes) or homozygous (genetic defect on both chromosomes) inherited. Men are twice as likely to be affected as women. The disease is usually noticeable from the age of 40 years.

In this form of porphyria, the fifth enzyme, uroporphyrinogen decarboxylase, is affected by the disorder. People with this defect often do not notice the disease. Only when the liver is heavily used, complaints are triggered. Alcohol is responsible for overuse of the liver in two-thirds of the cases. But there are also other triggers such as drugs, such as estrogens in the contraceptive pill.

Erythropoietic Protoporphyria (EPP)

In rare erythropoietic protoporphyria, the enzyme defect lies in the last step of heme formation, the incorporation of the iron ion. The consequence is above all a strong photosensitivity of the skin. Erythropoietic protoporphyria often occurs for the first time in childhood.

Porphyria: examinations and diagnosis

Due to the complexity of the disease and the many-sided symptoms, it may also be for one experienced doctor difficult to be the right diagnosis. Especially important are the typical porphyria symptoms as well as information about similar diseases in relatives. For accurate porphyria diagnosis, blood, urine and stool for porphyrins are examined. The best way to do this is when the person is experiencing ailments, as the values ​​in the course of the disease can change and even drop to a normal level. Further important diagnostic steps in the diagnosis of porphyria:

Acute intermittent porphyria (AIP)

In the case of acute intermittent porphyria, the urine turns red to dark red on prolonged standing. This proof succeeds however only with two thirds of the cases. Another screening test is the reverse Ehrlich aldehyde sample. One drop of urine is added to one milliliter of Ehrlich's reagent. If there is an acute intermittent porphyria, a cherry red color results.

Porphyria cutanea tarda

Characteristic is an enlarged liver, which is usually palpable. When ultrasound examination is usually a fatty liver or liver cirrhosis to detect. In addition, a liver biopsy can be revealing. A small tissue sample of the liver is taken under local anesthesia with a hollow needle. Under a UV lamp, the tissue sample fluoresces red in Porphyria cutanea tarda. When subsequently examined with a microscope, an increased accumulation of iron (iron storage disease = siderosis), fatty liver, chronic liver inflammation or cirrhosis of the liver can sometimes be detected.

Erythropoietic Protoporphyria (EPP)

The symptoms described often already give rise to the suspicion of erythropoietic protoporphyria. This suspicion can be confirmed by a blood analysis. It examines heparin blood, that is, uncoagulated blood from red blood cells and blood plasma, to free protoporphyrin, a precursor of heme. Sometimes stool samples are also tested for protoporphyrin.

Porphyria: treatment

It is important to differentiate the different porphyrias as they are treated differently. For all: The respective enzyme defect is genetically determined and is therefore not curable. The therapy is therefore symptomatic, that is, only the symptoms can be alleviated. The aim is also to avoid triggering factors (exposure prophylaxis).

Acute intermittent porphyria (AIP)

If the diagnosis is confirmed and if there are serious episodes, the person concerned may need intensive medical supervision, as there is a risk of respiratory paralysis. Triggers of an acute episode such as certain medications must be discontinued. Additionally, glucose or heme arginine is infused, resulting in the elimination of enriched heme precursors. For reassurance and against the pain, patients are treated, for example, with salicylates and morphine derivatives. For tachycardia and hypertension help so-called b-receptor blockers (beta-blockers) and reserpine.

Porphyria cutanea tarda

In the case of Porphyria cutanea tarda, a consistent renunciation of the triggering factors such as alcohol and estrogen (as in the pill) can improve the symptoms. In addition, sufferers should protect themselves with sunscreen and clothing from the sun.

It may also be helpful to have a bloodletting in which 500 milliliters of blood are drained once a week. The aim is to flush out the accumulated porphyrin from the liver. With a total bleeding of four to eight liters, the condition of the patients normalizes in most cases. Patients should drink at least one and a half liters daily in order to compensate for the fluid loss. If liver cirrhosis is present, no bloodletting should be performed, as it would cause too many proteins to be lost.

In severe cases chloroquine therapy is recommended. Chloroquine, originally a drug used to treat malaria, binds the porphyrin, which is excreted by the kidneys. Thus, porphyrin can be well removed from the body.With good liver function, a chloroquine dose of 500 milligrams per day for one week is recommended.

Erythropoietic Protoporphyria (EPP)

Important measures are light protection through clothing and special sunscreen creams as well as the avoidance of triggering factors (such as alcohol, medicines).

A phototherapy with the dermatologist in the spring can make the skin more tolerant of sunlight: The skin is gently irradiated several times a week with artificial UV light. This makes her a little thicker and gives her a light complexion.

Some sufferers may relieve the symptoms of erythropoietic protoporphyria by taking beta-carotene, an orange natural dye. It can neutralize the reactive oxygen in the skin that is created by light and improve the symptoms. By taking the skin turns but usually slightly orange.

The drug afamelanotide is a new therapy and stimulates the tanning of the skin. It is increasingly the skin pigment melanin formed, which is stored in the skin. High levels of melanin in the skin can increase the amount of time the sun can expose the person. Afamelanotide shows good results and can significantly improve the quality of life. However, this drug is not yet approved in Germany.

If liver cirrhosis develops, a liver transplant must be considered.

Porphyria: Prevention

Porphyria can not be prevented because the disease is genetic. However, sufferers can do something themselves to prevent porphyria symptoms.

Acute intermittent porphyria (AIP)

Most acute relapses can be avoided by taking consistent precautions.

drugs: Certain medications can trigger an acute episode. Therefore, talk to your doctor before taking any medication and also when using home remedies or plant substances. It is best to completely abstain from medication. If this is not possible, for example, in the case of a serious illness, the physician will prescribe suitable medications after weighing the benefits and risks and with the agreement of a porphyria specialist.

alcohol: Patients are strongly advised against any alcohol intake. For some it can be very difficult to do without alcohol in the long term. However, you have to keep in mind that every boost can potentially be life-threatening.

nutrition: Diets or fasting can lead to an acute boost. It is therefore very important to pay attention to a regular diet and to maintain its weight. Patients with severe porphyria who have already had multiple relapses should be assisted by their doctor and nutritionist.

Porphyria cutanea tarda and erythropoietic protoporphyria (EPP)

Important in both porphyria forms is to avoid the sun as much as possible:

dressA simple sun protection measure is to wear long-sleeved, tightly woven clothing, a hat, closed shoes and gloves.

suncream: Normal sunscreens are not suitable as they absorb the light in the UV range, but not the blue portion of the visible light, which also damages the skin. You should therefore only use special sunscreen creams based on titanium dioxide and zinc oxide as these protect against UVA, UVB and visible light.

These simple measures can reduce the risk of porphyria. Most sufferers only have one to two relapses in their lives. The risk of a relapse decreases with age - however, porphyria never disappears completely.

Read more about the investigations

  • blood collection
  • blood test

Porphyria: disease course and prognosis

The severity of porphyria varies. For most sufferers a largely normal life is possible if they pay attention to certain things. Others suffer from severe, painful photosensitivity and liver dysfunction.

Acute intermittent porphyria (AIP)

Most sufferers who experience one or more relapses recover completely and only have to take care of a few precautions. In less than ten percent of cases, recurrent episodes often occur. If it comes to paralysis, it may take several weeks to many months before they regress.

Erythropoietic Protoporphyria (EPP)

Patients with EPP should go to the doctor regularly (at least once a year) to have their blood tested for possible damage from accumulated porphyrin. This is rare, but should be recognized as early as possible, because erythropoietic protoporphyria is fatal in ten percent of cases.

Porphyria cutanea tarda

The course of this porphyria form is usually favorable, but depends on how much the liver is damaged and whether certain drugs (as a trigger) consistently avoided.

Patients with this form of porphyria have an increased risk of liver cell cancer.

These laboratory values ​​are important

  • bilirubin

Porphyria

FAQ - 💬

❓ What happens when you have porphyria?

👉 These disorders are usually inherited, meaning they are caused by gene mutations link passed from parents to children. If you have porphyria, cells fail to change chemicals in your body—called porphyrins and porphyrin precursors—into heme, the substance that gives blood its red color.

❓ What is porphyria and how is it treated?

👉 Treatment of cutaneous porphyrias focuses on reducing exposure to triggers such as sunlight and reducing the amount of porphyrins in your body to help eliminate your symptoms. This may include: Periodically drawing blood (phlebotomy) to reduce the iron in your body, which decreases porphyrins.

❓ What causes porphyria attacks?

👉 Acute porphyria refers to a group of rare disorders characterized by an enzymatic defect in the heme biosynthetic pathway. [1][2] Patients present with acute debilitating, life-threatening attacks that may be precipitated by medications, hormonal changes, starvation, and other factors.

❓ What is the life expectancy of someone with porphyria?

👉 19. What is the life expectancy for people with porphyria? This depends upon the specific type of porphyria and the severity. For most patients, the life expectancy is similar to that of persons without porphyria.

❓ Where is porphyria most common?

👉 Acute intermittent porphyria is the most common form of acute porphyria in most countries. It may occur more frequently in northern European countries, such as Sweden, and in the United Kingdom. Another form of the disorder, hereditary coproporphyria, has been reported mostly in Europe and North America.

❓ When should you suspect porphyria?

👉 Constipation and hyponatremia are common during these acute attacks. The diagnosis of acute porphyria should be suspected, especially in women who present symptoms linked to their menstrual cycles more than once in the ED. Once suspected, the diagnosis of porphyria can be rapidly established by measuring urinary PBG.

❓ What does porphyria pain feel like?

👉 The most commonly reported debilitating symptoms are diffuse severe pain affecting the abdomen, back, or limbs; other common attack signs and symptoms include nausea and vomiting, constipation, hypertension, motor weakness, insomnia, or anxiety [1–3, 5].

❓ What is the most common porphyria?

👉 Acute intermittent porphyria (AIP) is the most common of the acute porphyrias. Symptoms include periodic attacks, as described above. Long-term complications of AIP and other acute porphyrias may include progressive kidney damage, high blood pressure and liver cancer.

❓ What drugs can cause porphyria?

👉 In general, drugs that lead to increased activity of the hepatic P450 system, such as phenobarbital, sulfonamides, estrogens, and alcohol, are associated with porphyria.

❓ What color is urine in porphyria?

👉 The terms porphyrin and porphyria are derived from the Greek word porphyrus, meaning purple. Urine from porphyria patients may be dark or reddish in color due to the presence of excess porphyrins and related substances, and may darken further after exposure to light.

❓ What is porphyria of the liver?

👉 Porphyria is a group of liver disorders in which substances called porphyrins build up in the body, negatively affecting the skin or nervous system. The types that affect the nervous system are also known as acute porphyria, as symptoms are rapid in onset and short in duration.

❓ What are the symptoms of porphyria?

👉 Symptoms of porphyria can vary widely in severity, by type and among individuals. Some people with the gene mutations that cause porphyria never have any symptoms. Acute porphyrias include forms of the disease that typically cause nervous system symptoms, which appear quickly and can be severe.

❓ Can porphyria be inherited?

👉 One common type of cutaneous porphyria, known as porphyria cutanea tarda, is sometimes passed through genes but can also be what doctors call an "acquired disease." In that case, certain conditions or actions can trigger symptoms of porphyria.

❓ How does protoporphyria affect the body?

👉 In people with protoporphyria, bile carries extra porphyrins from the liver to the gallbladder, which may lead to gallstones that are made of porphyrins. Two types of cutaneous porphyria, congenital erythropoietic porphyria and, less commonly, hepatoerythropoietic porphyria, may cause severe anemia.


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