Porphyrias are a group of rare inherited blood disorders. People with these disorders have problems making a substance called heme in their bodies. Heme is made of body chemicals called porphyrin, which are bound to iron.
Heme is a component of hemoglobin, a protein in red blood cells that carries oxygen. It helps red blood cells carry oxygen and gives them their red color.
Heme is also found in myoglobin, a protein in the heart and skeletal muscles.
The body goes through several steps to make heme. In people with porphyria, the body lacks certain enzymes needed to complete this process.
This causes porphyrin to accumulate in tissues and blood, which may cause a variety of symptoms, ranging from mild to severe.
The most common symptoms of porphyria are:
- abdominal pain
- light sensitivity
- problems with the muscles and nervous system
The symptoms of porphyria vary and depend on which enzyme is missing.
There are several types of porphyria, which are classified into two categories:
Hepatic forms of the disorder are caused by problems in the liver. They’re associated with symptoms such as abdominal pain and problems with the central nervous system.
Erythropoietic forms are caused by problems in red blood cells. They’re associated with light sensitivity.
Delta-aminolevulinate-dehydratase deficiency porphyria
ALAD porphyria (ADP) is a deficiency of the enzyme delta-aminolevulinic acid (ALA) and is one of the more severe and rare forms of porphyria. Only about 10 cases have been reported worldwide, and all have been in males.
Symptoms present as an acute attack, often as severe abdominal cramping with vomiting and constipation.
Acute intermittent porphyria
Acute intermittent porphyria (AIP) is a deficiency of the enzyme hydroxymethylbilane synthase (HMBS). Many with an HMBS gene mutation don’t show symptoms unless triggered by one or more of the following:
- hormonal changes
- certain drug usage
- alcohol consumption
- dietary changes
Women going through puberty are especially likely to have symptoms. These may include:
- pain in the arms and legs
- muscle weakness
- confusion, hallucinations, and seizures
- heart palpitations
Hereditary coproporphyria (HCP) is characterized by a deficiency of the enzyme coproporphyrinogen oxidase (CPOX).
Similar to AIP, symptoms may not occur unless triggered by behavioral, environmental, or hormonal changes.
Both men and women are affected equally, though women are more likely to experience symptoms.
Attacks can include symptoms such as:
- acute abdominal pain
- pain or numbness in the arms and legs
- high blood pressure
Symptoms can vary greatly including skin symptoms, neurological symptoms, or both. Sun sensitivity including blistering skin is the most common skin symptom of Variegate porphyria (VP).
Acute attacks of VP often begin with abdominal pain.
Congenital erythropoietic porphyria
Congenital erythropoietic porphyria (CEP) results from the deficient function of the enzyme uroporphyrinogen lll cosynthase (UROS).
The most common symptom is hypersensitivity of the skin to sunlight and some forms of artificial light. Blistering and lesions can often occur from exposure.
CEP is a very rare disorder with just over 200 cases having been reported worldwide.
Porphyria cutanea tarda
According to the American Porphyria Foundation, Porphyria cutanea tarda (PCT) is the most common type of porphyria. It’s associated with extreme sensitivity to sunlight and painful, blistering lesions on the skin.
PCT is mostly an acquired disease, but some people have a genetic deficiency of the enzyme uroporphyrinogen decarboxylase (UROD) that contributes to the development of PCT.
Men and women can both be affected, but PCT is most common in women over age 30.
Hepatoerythropoietic porphyria (HEP) is the autosomal recessive form of familial porphyria vutanea tarda (f-PCT) and presents with similar symptoms.
Skin sensitivity to light often leads to severe blistering, sometimes with mutilation or loss of fingers or facial features. Skin symptoms usually begin in infancy.
People may also experience hair growth (hypertrichosis), brown- or red-colored teeth (erythrodontia), and red- or purple-colored urine.
HEP is very rare, with only about 40 cases reported worldwide.
Erythropoietic protoporphyria (EPP) is an inherited metabolic disorder causing skin hypersensitivity to light. The skin often becomes itchy and red after exposure and a burning sensation can occur.
Onset usually begins in infancy and is the most common porphyria in children. Though both men and women can experience EPP symptoms, it’s often more servere in men.
Symptoms depend on the type of porphyria. Severe abdominal pain is present in all types, as well as urine that’s reddish-brown in color. This is caused by the buildup of porphyrins and typically occurs after an attack.
Symptoms associated with hepatic disease include:
- limb pain
- tachycardia (fast heart rate)
- electrolyte imbalance
Symptoms associated with erythropoietic disease include:
- extreme skin sensitivity to light
- anemia (when the body does not produce enough new red blood cells)
- changes in skin pigmentation
- erratic behavior related to sun exposure
There’s no cure for porphyria. Treatment focuses on managing symptoms. Most cases are treated with medication.
Treatments for hepatic disease include:
- beta-blockers, such as Atenolol, to manage blood pressure
- high carbohydrate diet to aid recovery
- opioids for pain management
- hematin to shorten attacks
- gene therapies, such as givosiran
The treatment was determined to have decreased the rate at which the liver produces toxic byproducts, leading to less attacks.
Treatments for erythropoietic disease include:
- iron supplements for anemia
- blood transfusions
- bone marrow transplant
Porphyria is a genetic disease. According to the National Institutes of Health (NIH), most types of porphyria are inherited from an abnormal gene, called a gene mutation, from one parent.
However, certain factors may trigger symptoms of porphyria, known as attacks. Factors include:
- use of certain medications
- use of hormones, such as estrogen
- alcohol use
- exposure to sunlight
- dieting and fasting
Many tests can help diagnose this condition.
Tests that look for physical problems include:
- computed tomography (CT) scan
- chest X-ray
- echocardiogram (EKG)
Tests for blood problems include:
- urine test for fluorescence
- porphobilinogen (PBG) urine test
- complete blood count (CBC)
Porphyria is incurable and difficult to manage. Complications are common. They include:
- respiratory failure
- liver disease and failure
- skin scarring
Porphyria cannot be prevented. However, symptoms can be reduced by avoiding or eliminating triggers.
Factors that should be eliminated include:
- recreational drugs
- mental stress
- excessive drinking
- certain antibiotics
Preventing erythropoietic symptoms focuses on reducing light exposure by:
- staying out of bright sunlight
- wearing long sleeves, hats, and other protective clothing while outside
- asking for protection during surgery (in rare cases phototoxic injury can occur; this happens when light perforates the organs and leads to infection)
Long-term outlook varies widely, but treatments are being investigated every day. If you manage your symptoms and avoid triggers, you can carry out your everyday activities with few issues.
Getting a treatment plan in place early can help prevent permanent damage. Long-term damage can include:
- breathing difficulties requiring continuous oxygen
- walking problems
- anxiety attacks
Early diagnosis can help you lead a relatively normal life. Management is also very important.
If you have an inherited condition, talk to a genetic counselor. They can help you understand the risk of passing it to your children.