Variegate porphyria with coexistent decrease in porphobilinogen deaminase activity.
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.
Weinlich
G
G
Department of Dermatology, University of Innsbruck, Austria. georg.weinlich@uibk.ac.at
Doss
M O
MO
Sepp
N
N
Fritsch
P
P
D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D005420:Flavoproteins; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics*; D024101:Mitochondrial Proteins; D020125:Mutation, Missense / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010375:Pedigree; D017118:Porphyria, Acute Intermittent; D017094:Porphyrias, Hepatic / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D011166:Porphyrins / Q000378:metabolism; D050768:Protoporphyrinogen Oxidase
D005420:Flavoproteins; D024101:Mitochondrial Proteins; D011166:Porphyrins; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C493978:PPOX protein, human; D050768:Protoporphyrinogen Oxidase; D011163:Hydroxymethylbilane Synthase