The
porphyrias are a group of metabolic disorders that are caused by defects in
heme biosynthesis pathway
enzymes. The result is accumulation of
heme precursors, which can cause neurovisceral and/or cutaneous photosensitivity. Liver is commonly either a source or target of excess
porphyrins, and
porphyria-associated hepatic dysfunction ranges from minor abnormalities to
liver failure. In this review, the first of a three-part series, we describe the defects commonly found in each of the eight
enzymes involved in
heme biosynthesis. We also discuss the pathophysiology of the
hepatic porphyrias in detail, covering epidemiology, histopathology, diagnosis, and complications. Cellular consequences of
porphyrin accumulation are discussed, with an emphasis on oxidative stress,
protein aggregation,
hepatocellular cancer, and endothelial dysfunction. Finally, we review current
therapies to treat and manage symptoms of
hepatic porphyria.