Beginning in her 20s, this 70-year-old female experienced episodes of abdominal pain accompanied by nausea, fatigue, and fecal and urinary urgency. Porphyria was considered in her 30s, but urine porphobilinogen (PBG) was normal. At age 60, she developed blistering on sun-exposed skin when taking an estrogen-medroxyprogesterone combination for menopausal symptoms. Laboratory findings suggested porphyria cutanea tarda (PCT), including: a) elevated urine porphyrins, predominance of uroporphyrin and heptacarboxyl porphyrin and an increased uroporphyrin/coproporphyrin ratio, b) normal urine PBG, c) elevated total fecal porphyrins and isocoproporphyrin/coproporphyrin ratio, and d) normal erythrocyte uroporphyrinogen decarboxylase (UROD) activity. Four phlebotomies over 2 years reduced serum ferritin levels and achieved clinical remission. A variety of intermittent neurovisceral symptoms continued. At age 64, findings were diagnostic for variegate porphyria (VP), with: a) intermittent PBG elevation, b) elevated urine porphyrins (predominantly coproporphyrin III), c) elevated fecal porphyrins with an increased coproporphyrin III/I ratio and d) normal total plasma porphyrins but a peak fluorescence at 626 nm at neutral pH. Mutation analysis revealed a protoporphyrinogen oxidase (PPOX) gene mutation (c.1123C>T, p.375*), previously associated with VP, and predicted to result in premature protein termination. She has since been hospitalized several times for acute attacks, and treated with hemin. Prophylactic hemin was partially successful in preventing attacks.

This case is consistent with reports from South Africa and elsewhere that some VP patients may, usually early in their course, develop biochemical and clinical features of PCT. Although rarely recognized, this may occur more often than expected, and suggests that VP may predispose to reversible inhibition of hepatic UROD by a mechanism that remains to be elucidated.