A plasma scan and a DNA result were available for comparison in 679 individuals, of whom 205 carried a VP-associated PPOX mutation: R59W (n = 190), 537delAT (n = 14), or c769delG; 770T>A (n = 1).
Of 22 others who carried a PPOX mutation but had no plasma porphyrin fluorescence peak and whose fecal porphyrin results were available, none had evidence of VP by fecal analysis.
Direct comparison of plasma scanning and fecal porphyrin analysis was possible in 168 adults, of whom 73 carried a VP-associated PPOX mutation, for whom both tests were available.
In Tables 2 and 4, sensitivity was calculated separately for symptomatic and asymptomatic individuals in the subgroup of individuals carrying a VP-associated PPOX mutation for whom clinical information was available.
12), who characterized inheritance of VP on the basis of lymphocyte PPOX activities and reported a sensitivity of ~0.
Our results suggest that the sensitivities of both tests may be lower in asymptomatic individuals with PPOX mutations screened on the basis of a family history than they are in individuals with symptomatic VP.
Although our experience suggests that plasma scanning may in some instances identify carriers of a PPOX mutation before puberty, neither scanning nor fecal analysis is sufficiently sensitive for the exclusion of the carrier state, particularly in children.
1) Nonstandard abbreviations: VP, variegate porphyria; PPOX, protoporphyrinogen oxidase; AIP, acute intermittent porphyria; PCT, porphyria cutanea tarda; AUC, area under the curve; and CI, confidence interval.
Five different PPOX gene sequence variations were detected in this study (Table 1).
However, generation of a cryptic acceptor splice site in PPOX by substitution of the nucleotide positioned in IVS7-9 has been reported, which apparently leads to the synthesis of an abnormal mRNA in which 8 by of the intron sequence are maintained in the mRNA (3).
However, the fact that several missense mutations identified in the PPOX gene to date appear to be common polymorphic variations underscores that interpretations are to be made with caution.
Sequence variation, position, and predicted impact of the five PPOX mutations identified.