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

HB Anderson, MH Storandt, R Kallamadi, D Bande… - Cureus, 2021 - ncbi.nlm.nih.gov
HB Anderson, MH Storandt, R Kallamadi, D Bande, A Matta
Cureus, 2021ncbi.nlm.nih.gov
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 …
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.
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