Homozygous variegate porphyria: a compound heterozygote with novel mutations in the protoporphyrinogen oxidase gene

Homozygous variegate porphyria results from mutations in both alleles of th e protoporphyrinogen oxidase (PPOX) gene. Our patient, a 36-year-old woman, has severe cutaneous manifestations. Her clinical and biochemical features are similar to the few other reported cases, including onset before 18 mon ths of age, photosensitivity, absence of acute porphyric attacks, and eleva ted erythrocyte protoporphyrin. Mutation analysis of the PPOX gene revealed an in-frame 12 bp insert (c. 657-658 ins AAGGCCAGCGCC) encoding lysine-ala nine-serine-alanine (KASA), and a G to A transition at the splice donor sit e of exon 11 (TVS 11-1 G-->A). Neither of these mutations has been reported previously Our patient's mother has the spice site mutation and has had ac ute porphyric episodes. A maternal first cousin has the same mutation but n o clinical manifestations. The medical and family history of our patient's father is uncertain.