Conditions · Metabolism: heme, bilirubin and iron
Erythropoietic protoporphyria !
An inherited porphyria that causes burning skin pain within minutes of sun exposure, starting in childhood.
Updated 2026-11-01
Structures involved
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In biochemistry
- Heme synthesis: Step 1 · ALA synthase (ALAS1 liver, ALAS2 erythroid)
- Heme synthesis: Step 8 · Ferrochelatase
- ALA synthase
- Ferrochelatase
- Protoporphyrin IX
What it is
A cutaneous porphyria due to low ferrochelatase activity (or, in the X-linked form, excess ALAS2) that piles up free protoporphyrin in red cells, skin and liver.
Who gets it
It is the most common porphyria in children; symptoms begin in early childhood. It often goes undiagnosed for years because the skin looks almost normal.
Causes
- One non-functional FECH allele plus a common low-expression variant on the other
- X-linked protoporphyria: gain-of-function ALAS2 mutations
Risk factors
- Family history
- Strong sun exposure (also through window glass)
Pathophysiology
Iron-free protoporphyrin IX builds up in red cells and passes into the skin. When it absorbs visible light it generates reactive oxygen that damages dermal vessels: pain and swelling without blisters. It is hydrophobic and leaves through bile, where it can form stones and damage the liver.
Symptoms and signs
- Burning, stinging and itching of exposed skin minutes after sunlight
- Redness and swelling of the hands and face
- Thickened skin on the knuckles and fine scars on the nose
- Mild microcytic anemia
Diagnosis
- Clinical
- Immediate pain with sunlight since childhood, with few or no visible skin findings.
- Tests
- Markedly raised red-cell protoporphyrin, mostly free (metal-free); normal urine porphyrins; liver tests and ferritin; FECH and ALAS2 testing.
- Imaging
- Abdominal ultrasound to look for gallstones and signs of liver disease.
Treatment
- Lifestyle
- Protection from visible light: covering clothing, window films and zinc oxide or titanium dioxide sunscreens
- Medical
- Afamelanotide, a melanocyte-stimulating hormone analogue that raises sun tolerance
- Follow-up
- Regular monitoring of liver tests, iron and vitamin D
- Surgical
- Liver transplantation for protoporphyrin liver failure, followed by bone marrow transplantation to prevent recurrence
Complications
- Gallstones
- Cholestatic liver disease and liver failure (a few cases)
- Vitamin D deficiency
Test yourself
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Which enzyme fails in erythropoietic protoporphyria?
Ferrochelatase, the last step of heme synthesis.
Why are urine porphyrins normal in protoporphyria?
Protoporphyrin is hydrophobic and is excreted in bile, not urine.
How does the protoporphyria skin reaction differ from porphyria cutanea tarda?
Protoporphyria causes immediate pain without blisters; porphyria cutanea tarda causes blisters and fragility without immediate pain.
Related conditions
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Porphyria: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); FECH gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Porphyrins blood test: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); ALAS2 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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