RT Book, Section A1 Saavedra, Arturo P. A1 Roh, Ellen K. A1 Mikailov, Anar SR Print(0) ID 1199570802 T1 Genetic Diseases T2 Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology, 9e YR 2023 FD 2023 PB McGraw-Hill Education PP New York, NY SN 9781264278015 LK accessmedicine.mhmedical.com/content.aspx?aid=1199570802 RD 2024/03/29 AB Pseudoxanthoma elasticum (PXE) is a serious hereditary disorder of connective tissue that involves the elastic tissue in the skin, blood vessels, and eyes. Autosomal recessive (most common) and autosomal dominant. Incidence: 1:40,000 to 1:100,000.Etiology and Pathogenesis: Pathogenic mutation in the ABCC6 gene, which encodes MRP6, a member of the ATPase-dependent transmembrane transporter family of proteins. MRP6 can serve as an efflux pump transporting small-molecular-weight glutathione conjugates, which may facilitate calcification of elastic fibers. MRP6 is also thought to play a role in cellular detoxification.The principal skin manifestations are a distinctive peau d’orange surface pattern resulting from closely grouped clusters of yellow papules (cobblestoning) in a reticular pattern on the neck, axillae, and other body folds (Fig. 16-1).The effects on the vascular system include GI hemorrhage, hypertension occurring in young persons and resulting from involvement of renal arteries and claudication.Ocular manifestations (“angioid” streaks and retinal hemorrhages) can lead to blindness.Dermatopathology: Biopsy of a scar can detect characteristic changes of PXE before typical skin changes are apparent. Swelling and irregular clumping and basophilic staining of elastic fibers, which appear curled and “chopped up,” with calcium deposition.The course is inexorably progressive. Gastric artery hemorrhage → hematemesis. Peripheral vascular disease → cerebrovascular accidents, atherosclerosis obliterans, or bowel angina. Pregnancies are complicated by miscarriage and cardiovascular complications. Blindness. Life span is often shortened resulting from myocardial infarction or massive GI hemorrhage.Management: Genetic counseling. Evaluate family members for PXE. Regular re-evaluation by primary care physician and ophthalmologist is mandatory.Support organization: PXE International, www.pxe.org