Pseudoxanthoma elasticum

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.

Intra-operative radiotherapy management for breast cancer treatment in patients with pseudoxanthoma elasticum: A case report

“…This gene encodes for the eponymous membrane transport protein. The presence of a specific mutation (more than 60 are described) causes a reduction or absence leads to accumulation of extracellular material (calcium hydrogen phosphate and calcium hydroxyapatite) and, to a lesser extent, iron precipitates …”

“…The most frequent appearances are small yellow and narrow papules in areas of major skin mobility, retinal vascular strokes; moreover, there is tendency to gastrointestinal bleeding and arterial insufficiency. The lesions of the skin may appear in the second decade and increase in number and gravity during the adolescence …”

“…The presence of a specific mutation (more than 60 are described) causes a reduction or absence leads to accumulation of extracellular material (calcium hydrogen phosphate and calcium hydroxyapatite) and, to a lesser extent, iron precipitates. 1 The clinical frequency has been estimated to be 1:25 000-1:100 000; the ratio female/male is 2:1.…”

“…The lesions of the skin may appear in the second decade and increase in number and gravity during the adolescence. 1,2 Unfortunately, most pathological effects are irreversible, but prophylactic measures can be taken to prevent or minimize signs and symptoms, especially cardiovascular involvement.…”

A Case of Skin Laxity

“…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. 2 …”