The prevalence of pseudoxanthoma elasticum: Revised estimations based on genotyping in a high vascular risk cohort

Background: Pseudoxanthoma elasticum (PXE), an autosomal recessive systemic calcification disorder, is caused by mutations in the ABCC6-gene and associated with severe visual impairment and peripheral arterial disease. Given the progress in development of a therapy for PXE, more precise estimations of its prevalence are warranted. Methods: We genotyped the four most common ABCC6 mutations (c.3421C > T, c.4182delG, c.3775delT, c.2787+1G > T), together accounting for half of all ABCC6 mutations identified in PXE patients from the Dutch population, in a Dutch high vascular risk cohort (n = 7893). The obtained allele frequencies were used to estimate the prevalence of PXE using the Hardy-Weinberg equilibrium. Results: The carrier frequency of ABCC6 was 0.60% for c.3421C > T, 0.17% for c.4182delG, 0.05% for c.3775delT and 0.03% for c.2787+1G > T. The prevalence of PXE based upon the allele frequencies of these four mutations was estimated as 1 per 56,000 (95%CI 1 per 35,000–97,000). Conclusion: The prevalence of PXE is at least 1 per 56,000 meaning that there would be at least 307 affected individuals in the Netherlands that may benefit from a potential upcoming treatment. Since this estimate is based on mutations together accounting for half of all ABCC6 mutations identified among PXE patients, the actual prevalence will probably be higher.