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Orphanet Journal of Rare Diseases May 2017Pseudoxanthoma elasticum (PXE) is a genetic metabolic disease with autosomal recessive inheritance caused by mutations in the ABCC6 gene. The lack of functional ABCC6... (Review)
Review
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.
Topics: Animals; Choroidal Neovascularization; Diphosphates; Humans; Metabolic Diseases; Peripheral Arterial Disease; Pseudoxanthoma Elasticum; Skin
PubMed: 28486967
DOI: 10.1186/s13023-017-0639-8 -
Handbook of Clinical Neurology 2015Pseudoxanthoma elasticum (PXE) is characterized by elastic tissue fragmentation and calcification. The deterioration of elastic fibers leads to characteristic yellowish... (Review)
Review
Pseudoxanthoma elasticum (PXE) is characterized by elastic tissue fragmentation and calcification. The deterioration of elastic fibers leads to characteristic yellowish papules and plaques (pseudoxanthomas) and retinal angioid streaks. Although these findings may begin in childhood, the diagnosis is typically not made until the second or third decade after the skin and retinal findings become more prominent. Cerebrovascular complications include brain infarction due to narrowing and occlusion of cerebral arteries and aneurysm formation. Intracranial hemorrhage can occur in the absence of aneurysm, and gastrointestinal hemorrhage is common. Peripheral arterial vascular disease can lead to intermittent leg claudication. A skin biopsy often demonstrates calcified elastic fibers, even in a mildly affected area of skin. The inheritance is autosomal recessive, although heterozygotes may exhibit some features of the disease. PXE is due to mutation of the ABCC6 gene on chromosome 16. There is no treatment, but certain lifestyle modifications may limit the complications. The potential for retinal hemorrhage has led to recommendations for limitations of contact sports or other activities that might facilitate eye trauma. Other recommendations include maintaining a normal lipid profile, avoidance of aspirin and nonsteroidal anti-inflammatory agents, and limiting dietary calcium intake.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Multidrug Resistance-Associated Proteins; Mutation; Pseudoxanthoma Elasticum
PubMed: 26564082
DOI: 10.1016/B978-0-444-62702-5.00015-9 -
Retina (Philadelphia, Pa.) Dec 2019
Topics: Angioid Streaks; Humans; Retina
PubMed: 31592884
DOI: 10.1097/IAE.0000000000002660 -
Retina (Philadelphia, Pa.) Dec 2019
Topics: Angioid Streaks; Humans
PubMed: 31592883
DOI: 10.1097/IAE.0000000000002661 -
The Journal of the Royal College of... Jun 2022Pseudoxanthoma elasticum (PXE) is an autosomal recessive multisystem disorder showing phenotypic heterogeneity giving rise to complex comorbidities. The most 'visible'...
Pseudoxanthoma elasticum (PXE) is an autosomal recessive multisystem disorder showing phenotypic heterogeneity giving rise to complex comorbidities. The most 'visible' signs are dermatological; however, these may be subtle and hidden from the view of an affected individual. Ophthalmic signs can be easily missed, and here we highlight the importance of a multisystem assessment. We report a patient who developed advanced sight loss due to maculopathy whose underlying PXE aetiology went unnoticed until subtle skin signs were noticed on the lateral aspect of his neck. He was aware of the skin changes. Careful review of his previous retinal imaging showed the presence of 'angioid streaks' and anatomic alteration at the outer retina-Bruch membrane associated with his prior history of choroidal neovascularisation. The diagnosis was subsequently confirmed by skin biopsy and genetic testing. This case highlights the subtlety of both dermatological and ophthalmic signs in PXE.
Topics: Angioid Streaks; Biopsy; Humans; Male; Pseudoxanthoma Elasticum; Skin
PubMed: 36146987
DOI: 10.1177/14782715221103686 -
Advances in Experimental Medicine and... 2018Pseudoxanthoma elasticum (PXE) is an autosomal recessive multisystem disorder that involves the skin, GI tract, and heart, as well as the eye. It affects approximately 1... (Review)
Review
Pseudoxanthoma elasticum (PXE) is an autosomal recessive multisystem disorder that involves the skin, GI tract, and heart, as well as the eye. It affects approximately 1 in 50,000 people worldwide and is seen twice as frequently in females as in males. Fundus findings include angioid streaks (Fig. 38.1), reticular macular dystrophy, speckled appearance temporal to the macula (peau d'orange, like the dimpled texture of an orange peel), drusen of the optic nerve, and vitelliform-like deposits. Peau d'orange may precede the development of an angioid streak. "Comets," with or without a tail, are seen as solitary subretinal, nodular white bodies of retinal pigment epithelium (RPE) atrophy, usually present in the mid periphery (Fig. 38.2). The tail points toward the optic disc. Patients sometimes develop choroidal neovascular membrane. Skin changes (plucked chicken-like appearance) occur on the flexure areas, including the neck and axilla, as well as increased skin laxity with excessive skin folding. Cardiovascular changes include accelerated atherosclerosis with occlusive vascular disease leading to angina, hypertension, restrictive cardiomyopathy, mitral valve prolapse, and others. Progressive calcification and fragmentation of elastic fibers in the skin, eye, and cardiovascular system is the underlying pathophysiology.
Topics: Angioid Streaks; Female; Fluorescein Angiography; Fundus Oculi; Humans; Male; Metabolism, Inborn Errors; Pseudoxanthoma Elasticum
PubMed: 30578511
DOI: 10.1007/978-3-319-95046-4_38 -
QJM : Monthly Journal of the... Jul 2021
Topics: Angioid Streaks; Fluorescein Angiography; Humans; Pseudoxanthoma Elasticum
PubMed: 32502256
DOI: 10.1093/qjmed/hcaa190