Defects in HFE are a cause of porphyria cutanea tarda (pct), a disorder characterized by light-sensitive dermatitis and presence of large amounts of uroporphyrin in urine. Iron overload is often present in association with varying degrees of liver damage. pct is the most common form of porphyria worldwide. It occurs in two forms: the sporadic type (pct type i) and the familial type (pct type ii), which is inherited in an autosomal dominant manner.

Defects in HFE are a cause of variegate porphyria (vp), the most common form of porphyria in south africa. This autosomal dominant disease is characterized by skin hyperpigmentation and hypertrichosis, abdominal pain, tachycardia, hypertension and neuromuscular disturbances. High fecal levels of protoporphyrin and coproporphyrin, increased urine uroporphyrins and iron overload are typical markers of the disease.