FeCH

FECH is the gene that encodes ferrochelatase, the final enzyme of the heme biosynthesis pathway in humans. Ferrochelatase is a mitochondrial enzyme that inserts ferrous iron into protoporphyrin IX to form heme B, the prosthetic group required by hemoglobin, myoglobin, and various cytochromes. The reaction occurs in the mitochondrial matrix and connects the cytosolic steps of heme synthesis with mitochondrial handling of intermediates. FECH expression is widespread, with particularly high activity in tissues with active erythropoiesis, and the enzyme is highly conserved across species.

Genetic variants in FECH can cause hereditary disorders of heme biosynthesis. The most notable FECH-related condition is erythropoietic protoporphyria (EPP), which typically arises from a combination of a disease-causing FECH mutation on one chromosome and a common low-expression FECH allele on the other. Reduced ferrochelatase activity leads to accumulation of protoporphyrin IX, especially in erythrocytes and skin, producing photosensitivity and pain after light exposure. The inheritance is autosomal, but penetrance varies, and FECH variants can modify disease severity.

Diagnosis of FECH-related conditions relies on clinical features and biochemical testing showing elevated erythrocyte protoporphyrin, along with genetic testing confirming FECH variants. There is no cure; management focuses on sun protection and supportive care, while research continues into targeted therapies and the role of modifier alleles in disease expression.