CPOX

CPOX is the gene that encodes coproporphyrinogen oxidase, a mitochondrial enzyme involved in the third overall step of heme biosynthesis. In humans, the CPOX-encoded enzyme catalyzes the oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen IX, a reaction that requires molecular oxygen as part of the pathway that ultimately produces heme and its derivatives.

The CPOX enzyme is localized to the mitochondria, where it participates in the intracellular supply of protoporphyrin IX and heme. Proper function of this enzyme is essential for efficient heme production, which is required for various hemoproteins such as hemoglobin, cytochromes, and catalase.

Genetically, CPOX is a nuclear gene situated on chromosome 3 (3q12.2). Mutations in CPOX can cause hereditary coproporphyria (HCP), typically inherited in an autosomal dominant pattern with variable penetrance. Most pathogenic variants lead to reduced enzyme activity, resulting in accumulation of porphyrin precursors in the heme biosynthesis pathway.

Clinically, HCP presents mainly with neurovisceral symptoms during acute attacks, including abdominal pain, nausea, vomiting, neuropathies, and neuropsychiatric changes. Some individuals may also exhibit cutaneous photosensitivity due to porphyrin accumulation. Triggers such as drugs, fasting, infections, and hormonal changes can precipitate attacks.

Diagnosis is based on biochemical testing showing elevated urinary coproporphyrin levels and supportive porphyrin precursor profiles, along with genetic testing confirming CPOX variants. Management centers on avoiding triggers, treating symptoms during attacks, and administering hemin therapy in some cases to suppress endogenous heme synthesis. Genetic counseling is advised given the inheritance pattern.