Pseudoxanthoma elasticum pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ayokunle Olubaniyi, M.B,B.S [2]
Overview
Pseudoxanthoma elasticum involves the accumulation of calcium and fragmentation of elastin-containing fibers in the connective tissue, and in the mid-sized arteries. There is mutation of the ABCC6 gene which encodes for a transmembrane efflux transporter. Premature atherosclerosis is also associated with mutations in the ABCC6 gene. Recently, novel mutations have been found including p.R1141X and g.del23-29, and they account for about 40% of all mutations.
Pathophysiology
In PXE, there is calcification (accumulation of calcium) and fragmentation of the elastin-containing fibers in connective tissue, but primarily in the mid-sized arteries.[1] Strong genetic linkage was found with mutations in the ABCC6 gene but the exact mechanism by which this protein (which is a transmembrane efflux transporter from the large ATP-binding cassette transporter family) influences the disease course is unknown. The protein is expressed in most organs, but mainly in the liver and kidney. It is unclear in what way this would lead to abnormalities in skin, eyes and blood vessels. It is thought that some particular mutations do not cause a more severe or less severe form of the disease. Given the variations in age of onset and severity it is likely that other unknown risk factors (genetic and dietary) may be involved. Premature atherosclerosis is also associated with mutations in the ABCC6 gene, even in those without PXE.[2] A syndrome almost indistinguishable from hereditary PXE has been described in patients with hemoglobinopathies(sickle-cell disease and thalassemia) through a poorly understood mechanism. Recently, novel mutations have been found including p.R1141X and g.del23-29, and they account for about 40% of all mutations.[3] Mutations in the GGCX gene encoding vitamin K–dependent γ-glutamyl carboxylasehave have also been reported.[4]
References
- ↑ Gheduzzi D, Sammarco R, Quaglino D, Bercovitch L, Terry S, Taylor W, Ronchetti I (2003). "Extracutaneous ultrastructural alterations in pseudoxanthoma elasticum". Ultrastructural pathology. 27 (6): 375–84. PMID 14660276.
- ↑ Trip MD, Smulders YM, Wegman JJ; et al. (2002). "Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease". Circulation. 106 (7): 773–5. PMID 12176944.
- ↑ Uitto, J.; Váradi, A.; Bercovitch, L.; Terry, PF.; Terry, SF. (2013). "Pseudoxanthoma elasticum: progress in research toward treatment: summary of the 2012 PXE international research meeting". J Invest Dermatol. 133 (6): 1444–9. doi:10.1038/jid.2013.20. PMID 23673496. Unknown parameter
|month=ignored (help) - ↑ Berkner, KL. (2005). "The vitamin K-dependent carboxylase". Annu Rev Nutr. 25: 127–49. doi:10.1146/annurev.nutr.25.050304.092713. PMID 16011462.