Porphyria cutanea tarda (PCT) is the most common porphyria. It presents with photosensitivity, blistering skin lesions, and hypertrichosis. Urine shows elevated uroporphyrin. Which enzyme is deficient and which is the most common precipitant in adults?

• A Uroporphyrinogen decarboxylase (UROD); alcohol-related liver disease or hepatitis C virus (HCV) infection ✓
• B Coproporphyrinogen oxidase; iron overload alone
• C Hydroxymethylbilane synthase; estrogen therapy in post-menopausal women
• D Ferrochelatase; sun exposure directly activates the enzyme deficiency

Explanation

PCT results from UROD deficiency in the liver, leading to accumulation of highly carboxylated uroporphyrins (which absorb visible light and generate reactive oxygen species in skin). The sporadic (type I) form is acquired, most commonly triggered by alcohol, HCV infection, iron overload (haemochromatosis), or estrogens. Iron excess inhibits residual UROD activity by oxidising the enzyme's regulatory porphyrin substrate (uroporphyrinogen) to the inhibitory metabolite uroporphomethene. Erythropoietic protoporphyria involves ferrochelatase deficiency. Coproporphyrinogen oxidase deficiency causes hereditary coproporphyria, an acute porphyria.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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