UROD

UROD, or uroporphyrinogen decarboxylase, is an enzyme in the heme biosynthesis pathway. It resides in the cytosol and catalyzes the decarboxylation of the four acetate groups of uroporphyrinogen to form coproporphyrinogen, moving the pathway toward heme production. The enzyme acts on both isomers of uroporphyrinogen, but only the III isomer yields a productive route to heme.

Genetics and disease: The UROD gene encodes this enzyme. Partial hepatic UROD deficiency underlies porphyria cutanea tarda (PCT), typically autosomal dominant with incomplete penetrance. Severe, biallelic UROD mutations cause congenital erythropoietic porphyria (CEP), an autosomal recessive disorder with marked photosensitivity from infancy and, often, erythrodontia. PCT can also arise sporadically due to factors that inhibit UROD.

Clinical features and diagnosis: PCT presents with blistering and hyperpigmentation on sun-exposed skin; CEP shows more severe photosensitivity, anemia, and red-brown teeth. Laboratory testing reveals elevated urinary and plasma uroporphyrins. Confirmation is through UROD activity assays or genetic testing for UROD mutations.

Treatment and prognosis: PCT management includes phlebotomy to reduce iron stores and low-dose hydroxychloroquine to promote porphyrin excretion. CEP requires sun avoidance and supportive care; treatment is tailored to severity and genotype. Knowledge of UROD status informs family screening and counseling.