Iatrogenic Iron Overload Causing Porphyria Cutanea Tarda in a Patient With a Rare Nonsense Heterozygous UROD Gene Mutation

Abstract

Porphyria cutanea tarda (PCT) is a rare dermatologic condition characterized by blistering of sun-exposed surfaces and elevated hepatic enzymes. It may infrequently occur as the primary presentation of underlying hemochromatosis. A 61-year-old female with anemia caused by chronic kidney disease and end-stage renal disease on hemodialysis presented with a bullous rash on her hands with associated pruritus. The rash worsened despite conservative treatment. An initial biopsy demonstrated a pauci-inflammatory cell-poor subepidermal cleft. Subsequent workup revealed elevated serum and urine porphyrins, confirming a diagnosis of PCT. Additionally, her skin was darkened and ferritin was elevated. MRI of the liver demonstrated iron overload with genetic testing negative for C282Y or H63D mutations, supporting a diagnosis of secondary hemochromatosis. Further genetic testing revealed that the patient had a rare heterozygous nonsense mutation of the uroporphyrinogen decarboxylase (UROD) gene, for a sequence variant designated c.616C>T, which is predicted to result in premature protein termination (p.Gln206*). PCT occurs due to decreased function of UROD, leading to accumulation of porphyrins causing dermatologic manifestations and liver injury. UROD is inactivated in an iron-dependent process, explaining the mechanistic link between hemochromatosis and PCT.

Keywords: hemochromatosis; porphyria cutanea tarda; urod mutation.