Porphyria cutanea tarda (PCT) is the most common porphyria, presenting with photosensitive blistering skin lesions and hypertrichosis. Urine shows elevated uroporphyrins. The deficient enzyme and its biochemical consequence are:

• A Uroporphyrinogen decarboxylase (UROD) deficiency causing accumulation of uroporphyrinogen and heptacarboxyl porphyrins in skin and urine ✓
• B Ferrochelatase deficiency causing protoporphyrin IX accumulation with intense skin photosensitivity
• C Coproporphyrinogen oxidase deficiency causing faecal coproporphyrin elevation only
• D ALA synthase overactivity causing global porphyrin accumulation

Explanation

Uroporphyrinogen decarboxylase (UROD) catalyzes the sequential decarboxylation of the four acetic acid side chains of uroporphyrinogen III to form coproporphyrinogen III. UROD deficiency (sporadic or familial, precipitated by iron overload, alcohol, hepatitis C, and estrogens) causes accumulation of uroporphyrinogens and heptacarboxylporphyrins; these absorb light at 400 nm (Soret band), generating reactive oxygen species in the dermis causing fragile blistering skin. Iron is a critical cofactor for the enzymatic inactivation of UROD by uroporphomethene, explaining why venesection and low-dose chloroquine are therapeutic.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.