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Review
. 2017 May 10;12(1):85.
doi: 10.1186/s13023-017-0639-8.

Pseudoxanthoma elasticum

Dominique P Germain  1
Affiliations
Review

Pseudoxanthoma elasticum

Dominique P Germain. Orphanet J Rare Dis. .

Abstract

Pseudoxanthoma elasticum (PXE) is a genetic metabolic disease with autosomal recessive inheritance caused by mutations in the ABCC6 gene. The lack of functional ABCC6 protein leads to ectopic mineralization that is most apparent in the elastic tissues of the skin, eyes and blood vessels. The clinical prevalence of PXE has been estimated at between 1 per 100,000 and 1 per 25,000, with slight female predominance. The first clinical sign of PXE is almost always small yellow papules on the nape and sides of the neck and in flexural areas. The papules coalesce, and the skin becomes loose and wrinkled. The mid-dermal elastic fibers are short, fragmented, clumped and calcified. Dystrophic calcification of Bruch's membrane, revealed by angioid streaks, may trigger choroidal neovascularization and, ultimately, loss of central vision and blindness in late-stage disease. Lesions in small and medium-sized artery walls may result in intermittent claudication and peripheral artery disease. Cardiac complications (myocardial infarction, angina pectoris) are thought to be relatively rare but merit thorough investigation. Ischemic strokes have been reported. PXE is a metabolic disease in which circulating levels of an anti-mineralization factor are low. There is good evidence to suggest that the factor is inorganic pyrophosphate (PPi), and that the circulating low levels of PPi and decreased PPi/Pi ratio result from the lack of ATP release by hepatocytes harboring the mutant ABCC6 protein. However, the substrate(s) bound, transported or modulated by the ABCC6 protein remain unknown. More than 300 sequence variants of the ABCC6 gene have been identified. There is no cure for PXE; the main symptomatic treatments are vascular endothelial growth factor inhibitor therapy (for ophthalmic manifestations), lifestyle, lipid-lowering and dietary measures (for reducing vascular risk factors), and vascular surgery (for severe cardiovascular manifestations). Future treatment options may include gene therapy/editing and pharmacologic chaperone therapy.

Keywords: ABCC6; Angioid streak; Choroidal neovascularization; Ectopic mineralization; Metabolic disease; Peripheral arterial disease; Pseudoxanthoma elasticum; Skin.

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Figures

Fig. 1
Fig. 1
Characteristic cutaneous feature of PXE: yellow papules on the nape of the neck give the skin a peau d’orange aspect
Fig. 2
Fig. 2
Characteristic advanced cutaneous feature of PXE: involvement of axillary flexural folds
Fig. 3
Fig. 3
Characteristic histological features of PXE in skin biopsies. a Orcein staining: the elastic fibers of the dermis are fragmented and thickened. b Von Kossa staining: calcification of elastic fibers. c Viewed under the electron microscope, the elastic fibers’ morphology is abnormal
Fig. 4
Fig. 4
Characteristic ophthalmological feature of PXE: angioid streaks on the fundus
See this image and copyright information in PMC

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