Erythropoietic protoporphyria (EPP) causes severe burning photosensitivity in children exposed to sunlight. The enzyme defect leads to accumulation of protoporphyrin IX in red blood cells. Which enzyme is deficient in EPP?

• A Uroporphyrinogen decarboxylase (deficient in Porphyria Cutanea Tarda, PCT)
• B ALA synthase-2 (the erythroid-specific isoform, deficient in X-linked sideroblastic anaemia)
• C Ferrochelatase (which inserts Fe2+ into protoporphyrin IX to form haem) ✓
• D Coproporphyrinogen oxidase (deficient in hereditary coproporphyria)

Explanation

Ferrochelatase (FECH, the final step of haem synthesis) normally inserts ferrous iron (Fe2+) into protoporphyrin IX to form haem. In EPP, autosomal dominant (or recessive in some forms) FECH haploinsufficiency results in protoporphyrin IX accumulation in erythrocytes, plasma, and skin. Protoporphyrin IX is a cyclic porphyrin that absorbs light at ~400 nm (Soret band), generating singlet oxygen, causing immediate burning, erythema, and oedema in sun-exposed areas — the most painful of all cutaneous porphyrias. Uroporphyrinogen decarboxylase deficiency causes PCT (blistering photosensitivity, no neurological symptoms). ALA synthase-2 mutations cause X-linked sideroblastic anaemia.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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