Variegate porphyria is a
rare disease caused by a deficiency of
protoporphyrinogen oxidase. In most cases, the clinical findings are a combination of systemic symptoms similar to those occurring in
acute intermittent porphyria and cutaneous lesions indistinguishable from those of
porphyria cutanea tarda. We report on a 24-year-old woman with
variegate porphyria who, after intake of
lynestrenol, developed typical cutaneous lesions but no viscero-neurological symptoms. The diagnosis was based on the characteristic urinary coproporphyrin and faecal
protoporphyrin excretion patterns, and the specific peak of plasma fluorescence at 626 nm in spectrofluorometry. Biochemical analysis revealed that most of the family members, though free of clinical symptoms, excrete
porphyrin metabolites in urine and stool similar to
variegate porphyria, accompanied by a significant decrease of
porphobilinogen deaminase activity of a range which is ordinarily found in patients with
acute intermittent porphyria only (approximately 50%). These data first led to the assumption of two separate and independently inherited genetic defects, similar to the dual
porphyria of Chester. Molecular analysis, however, revealed only a missense mutation of the
protoporphyrinogen oxidase gene, but not of the
porphobilinogen deaminase gene. Thus, in the family presented,
porphobilinogen deaminase deficiency is likely to be a phenomenon secondary to the genetic defect of
protoporphyrinogen oxidase.