What Causes Porphyria?

Porphyrias are typically inherited, meaning a genetic mutation is passed on from at least one parent. In rare cases, porphyrias are acquired.

Porphyria refers to a group of disorders that are mostly inherited, usually affect the skin or nervous system, and are a result of defects in porphyrins (the enzymes involved in the production of heme, which is what gives blood its red color). 

Porphyria may occur in an acute or a chronic manner depending on the specific enzyme that is affected.

Types of acute porphyria (comes on suddenly, and usually severe) include:

• Acute intermittent porphyria 
• ALA dehydratase deficiency porphyria (Doss porphyria) 
• Hereditary coproporphyria 
• Variegate porphyria 

Types of chronic porphyria (lasts a long time, may come and go) include:

• Congenital erythropoietic porphyria 
• Erythropoietic porphyria 
• Porphyria cutanea tarda

Symptoms of acute porphyria attacks may include:

• Abdominal pain (most common symptom)
• Muscle weakness 
• Focal neurologic deficits such as muscle weakness affecting all four extremities (tetraparesis) 
• Psychiatric symptoms (such as psychosis and anxiety) 
• Abnormally colored urine (turns red or dark on exposure to light)
• Pain in the chest, limbs, or back
• Nausea and vomiting
• Constipation
• Urinary retention
• Confusion
• Hallucinations
• Seizures 

Symptoms of chronic porphyria usually involve the skin and may include:

• Photosensitivity (sensitivity of the skin to sunlight)
• Blisters on exposed areas of the skin 
• Itching and swelling on exposed areas of the skin

Porphyrias are typically inherited, meaning a genetic mutation is passed on from at least one parent. In rare cases, porphyrias are acquired. 

Porphyria cutanea tarda is usually an acquired disorder, not caused by genes. Causes of this type of porphyria include:

• Excess iron
• Use of alcohol 
• Estrogen use
• Smoking
• Chronic hepatitis C
• HIV/AIDS
• Genetic abnormalities associated with iron overload disease (hemochromatosis)

Symptoms of all types of porphyria may be triggered by:

• Alcohol use
• Smoking
• Certain medications or hormones
• Exposure to sunlight
• Stress
• Dieting/fasting

Tests of urine, blood, and stool are used to diagnose porphyrias, such as:

• Urine porphyrin studies 
• Plasma porphyrin level, using fluorescence emission spectroscopy
• Whole blood for porphyrin analysis 
• Stool studies 
• Erythrocyte uroporphyrinogen decarboxylase activity 

Treatment for acute porphyria episodes is aimed at relieving symptoms and may include:

• Parenteral narcotics for pain
• Hemin (plasma-derived intravenous heme) for management
• Avoidance of sunlight for cutaneous porphyrias
  • Afamelanotide, an alpha-melanocyte–stimulating hormone analogue, may allow the increased sun

Complications of acute intermittent porphyria include:

• Chronic high blood pressure (hypertension)
• Chronic kidney insufficiency
• Chronic pain syndrome
• Liver cancer (hepatocellular carcinoma)

Erythropoietic porphyria can cause severe pain and can be socially disabling, with a significant impact on the quality of life. Depression and anxiety can occur. 

Life expectancy depends on the type of porphyria. For many types, treatment works well and patients can live a normal life. 

Most types of porphyria are inherited, but attacks may be prevented in some cases. 

• Seek treatment in the early stages of an attack
• Don’t smoke
• Stay out of the sun