148
Views
62
CrossRef citations to date
0
Altmetric
Reviews

Pseudoxanthoma elasticum: diagnostic features, classification and treatment options

, MD PhD, , MD PhD, , PhD, , MD & , MA

Bibliography

  • Neldner KH. Pseudoxanthoma elasticum. Clin Dermatol 1988;6:1-159
  • Uitto J, Varadi A, Bercovitch L, et al. Pseudoxanthoma elasticum: progress in research toward treatment: summary of the 2012 PXE International Research Meeting. J Invest Dermatol 2013;133:1444-9
  • Darier J. Pseudo-xanthome élastique. III Congrès Intern de Dermat de Londres 1896;5:289-95
  • Grönblad E. Angioid streaks - pseudoxanthoma elasticum. Acta Ophthalmol 1929;7:329
  • Strandberg J. Pseudoxanthoma Elasticum. Z Haut Geschlechtskr 1929;31:689-94
  • Carlborg U. Study of circulatory disturbances, pulse wave velocity and pressure pulses in large arteries in cases of pseudoxanthoma elasticum and angioid streaks: a contribution to the knowledge of function of the elastic tissue and the smooth muscles in larger arteries. Acta Med Scan 1944;151:1-209
  • Uitto J, Li Q, Jiang Q. Pseudoxanthoma elasticum: molecular genetics and putative pathomechanisms. J Invest Dermatol 2010;130:661-70
  • Pfendner EG, Vanakker OM, Terry SF, et al. Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum. J Med Genet 2007;44:621-8
  • Chassaing N, Martin L, Calvas P, et al. Pseudoxanthoma elasticum: a clinical, pathophysiological and genetic update including 11 novel ABCC6 mutations. J Med Genet 2005;42:881-92
  • Walker ER, Frederickson RG, Mayes MD. The mineralization of elastic fibers and alterations of extracellular matrix in pseudoxanthoma elasticum. Ultrastructure, immunocytochemistry, and X-ray analysis. Arch Dermatol 1989;125:70-6
  • Kavukcuoglu NB, Li Q, Pleshko N, et al. Connective tissue mineralization in Abcc6(-/-) mice, a model for pseudoxanthoma elasticum. Matrix Biol 2012;31:246-52
  • Georgalas I, Papaconstantinou D, Koutsandrea C, et al. Angioid streaks, clinical course, complications, and current therapeutic management. Ther Clin Risk Manag 2009;5:81-9
  • Kornet L, Bergen AA, Hoeks AP, et al. In patients with pseudoxanthoma elasticum a thicker and more elastic carotid artery is associated with elastin fragmentation and proteoglycans accumulation. Ultrasound Med Biol 2004;30:1041-8
  • Lefthériotis G, Abraham P, Le Corre Y, et al. Relationship between ankle brachial index and arterial remodeling in pseudoxanthoma elasticum. J Vasc Surg 2011;54:1390-4
  • Goral V, Demir D, Tuzun Y, et al. Pseudoxantoma elasticum, as a repetitive upper gastrointestinal hemorrhage cause in a pregnant woman. World J Gastroenterol 2007;13:3897-9
  • van den Berg JSP, Hennekam RCM, Cruysberg JRM, et al. Prevalence of symptomatic intracranial aneurysm and ischaemic stroke in pseudoxanthoma elasticum. Cerebrovasc Dis 2000;10:315-19
  • Trip MD, Smulders YM, Wegman JJ, et al. Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease. Circulation 2002;106:773-5
  • Köblös G, Andrikovics H, Prohászka Z, et al. The R1141X loss-of-function mutation of the ABCC6 gene is a strong genetic risk factor for coronary artery disease. Genet Test Mol Biomarkers 2010;14:75-8
  • Campens L, Vanakker OM, Trachet B, et al. Characterization of cardiovascular involvement in pseudoxanthoma elasticum families. Arterioscler Thromb Vasc Biol 2013;33:2646-52
  • Pope FM. Historical evidence for the genetic heterogeneity of pseudoxanthoma elasticum. Br J Dermatol 1975;92:493-509
  • Miksch S, Lumsden A, Guenther UP, et al. Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6. Hum Mutat 2005;26:235-48
  • Ringpfeil F, McGuigan K, Fuchsel L, et al. Pseudoxanthoma elasticum is a recessive disease characterized by compound heterozygosity. J Invest Dermatol 2006;126:782-6
  • Lebwohl M, Neldner K, Pope FM, et al. Classification of pseudoxanthoma elasticum: report of a consensus conference. J Am Acad Dermatol 1994;30:103-7
  • Vanakker OM, Leroy BP, Coucke P, et al. Novel clinico-molecular insights in pseudoxanthoma elasticum provide an efficient molecular screening method and a comprehensive diagnostic flowchart. Hum Mutat 2008;29:205
  • Plomp AS, Toonstra J, Bergen AA, et al. Proposal for updating the pseudoxanthoma elasticum classification system and a review of the clinical findings. Am J Med Genet A 2010;152A:1049-58
  • Nitschke Y, Baujat G, Botschen U, et al. Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. Am J Hum Genet 2012;90:25-39
  • Li Q, Brodsky JL, Conlin L, et al. Mutations in the ABCC6 gene as a cause of generalized arterial calcification of infancy - genotypic overlap with pseudoxanthoma elasticum. J Invest Dermatol 2014;134:658-65
  • Ringpfeil F, Lebwohl MG, Christiano AM, et al. Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. Proc Natl Acad Sci USA 2000;97:6001-6
  • Bergen AA, Plomp AS, Schuurman EJ, et al. Mutations in ABCC6 cause pseudoxanthoma elasticum. Nat Genet 2000;25:228-31
  • Le Saux O, Urban Z, Tschuch C, et al. Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat Genet 2000;25:223-7
  • Struk B, Cai L, Zach S, et al. Mutations of the gene encoding the transmembrane transporter protein ABC-C6 cause pseudoxanthoma elasticum. J Mol Med (Berl) 2000;78:282-6
  • Li Q, Uitto J. Mineralization/anti-mineralization networks in the skin and vascular connective tissues. Am J Pathol 2013;183:10-18
  • Li Q, Sadowski S, Frank M, et al. The abcc6a gene expression is required for normal zebrafish development. J Invest Dermatol 2010;130:2561-8
  • Pomozi V, Brampton C, Fulop K, et al. Analysis of Pseudoxanthoma Elasticum-causing Missense mutants of ABCC6 in vivo; pharmacological correction of the mislocalized proteins. J Invest Dermatol 2014;Apr;134(4):946-53
  • Nitschke Y, Rutsch F. Generalized arterial calcification of infancy and pseudoxanthoma elasticum: two sides of the same coin. Front Genet 2012;3:302
  • Plomp AS, Bergen AA, Florijn RJ, et al. Pseudoxanthoma elasticum: wide phenotypic variation in homozygotes and no signs in heterozygotes for the c.3775delT mutation in ABCC6. Genet Med 2009;11:852-8
  • Lewis KG, Bercovitch L, Dill SW, et al. Acquired disorders of elastic tissue: part I. Increased elastic tissue and solar elastotic syndromes. J Am Acad Dermatol 2004;51:1-21
  • Kossard S. Pseudoxanthoma-like late-onset focal dermal elastosis. Australas J Dermatol 2005;46:47-50
  • Hamlin N, Beck K, Bacchelli B, et al. Acquired Pseudoxanthoma elasticum-like syndrome in beta-thalassaemia patients. Br J Haematol 2003;122:852-4
  • Nielsen AO, Christensen OB, Hentzer B, et al. Salpeter-induced dermal changes electron-microscopically indistinguishable from pseudoxanthoma elasticum. Acta Derm Venereol 1978;58:323-7
  • Sprecher E. Familial tumoral calcinosis: from characterization of a rare phenotype to the pathogenesis of ectopic calcification. J Invest Dermatol 2010;130:652-60
  • Nitschke Y, Rutsch F. Genetics in arterial calcification: lessons learned from rare diseases. Trends Cardiovasc Med 2012;22:145-9
  • Ruf N, Uhlenberg B, Terkeltaub R, et al. The mutational spectrum of ENPP1 as arising after the analysis of 23 unrelated patients with generalized arterial calcification of infancy (GACI). Hum Mutat 2005;25:98
  • Rutsch F, Nitschke Y, Terkeltaub R. Genetics in arterial calcification: pieces of a puzzle and cogs in a wheel. Circ Res 2011;109:578-92
  • Le Boulanger G, Labreze C, Croue A, et al. An unusual severe vascular case of pseudoxanthoma elasticum presenting as generalized arterial calcification of infancy. Am J Med Genet A 2010;152A:118-23
  • Chefetz I, Ben Amitai D, Browning S, et al. Normophosphatemic familial tumoral calcinosis is caused by deleterious mutations in SAMD9, encoding a TNF-alpha responsive protein. J Invest Dermatol 2008;128:1423-9
  • St Hilaire C, Ziegler SG, Markello TC, et al. NT5E mutations and arterial calcifications. N Engl J Med 2011;364:432-42
  • Vanakker OM, Martin L, Gheduzzi D, et al. Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity. J Invest Dermatol 2007;127:581-7
  • Li Q, Schurgers LJ, Smith AC, et al. Co-existent pseudoxanthoma elasticum and vitamin K-dependent coagulation factor deficiency: compound heterozygosity for mutations in the GGCX gene. Am J Pathol 2009;174:534-40
  • Berkner KL. The vitamin K-dependent carboxylase. Annu Rev Nutr 2005;25:127-49
  • Gheduzzi D, Boraldi F, Annovi G, et al. Matrix Gla protein is involved in elastic fiber calcification in the dermis of pseudoxanthoma elasticum patients. Lab Invest 2007;87:998-1008
  • Schurgers LJ, Uitto J, Reutelingsperger CP. Vitamin K-dependent carboxylation of matrix GLA-protein: a crucial switch to control ectopic mineralization. Trends Mol Med 2013;19:217-26
  • Borst P, van de Wetering K, Schlingemann R. Does the absence of ABCC6 (multidrug resistance protein 6) in patients with Pseudoxanthoma elasticum prevent the liver from providing sufficient vitamin K to the periphery? Cell Cycle 2008;7:1575-9
  • Jiang Q, Li Q, Grand-Pierre AE, et al. Administration of vitamin K does not counteract the ectopic mineralization of connective tissues in Abcc6-/- mice, a model for pseudoxanthoma elasticum. Cell Cycle 2011;10:701-7
  • Brampton C, Yamaguchi Y, Vanakker O, et al. Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum. Cell Cycle 2011;10:1810-20
  • Gorgels TG, Waarsing JH, Herfs M, et al. Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum. J Mol Med (Berl) 2011;89:1125-35
  • Fülöp K, Jiang Q, Wetering KV, et al. ABCC6 does not transport vitamin K3-glutathione conjugate from the liver: relevance to pathomechanisms of pseudoxanthoma elasticum. Biochem Biophys Res Commun 2011;415:468-71
  • Kovach JL, Schwartz SG, Hickey M, et al. Thirty-two month follow-up of successful treatment of choroidal neovascularization from angioid streaks with intravitreal bevacizumab. Ophthalmic Surg Lasers Imaging 2009;40:77-9
  • Sawa M, Gomi F, Tsujikawa M, et al. Long-term results of intravitreal bevacizumab injection for choroidal neovascularization secondary to angioid streaks. Am J Ophthalmol 2009;148:584-90. e2
  • Wiegand TW, Rogers AH, McCabe F, et al. Intravitreal bevacizumab (Avastin) treatment of choroidal neovascularisation in patients with angioid streaks. Br J Ophthalmol 2009;93:47-51
  • Georgalas I, Tservakis I, Papaconstaninou D, et al. Pseudoxanthoma elasticum, ocular manifestations, complications and treatment. Clin Exp Optom 2011;94:169-80
  • Renie WA, Pyeritz RE, Combs J, et al. Pseudoxanthoma elasticum: high calcium intake in early life correlates with severity. Am J Med Genet 1984;19:235-44
  • Klement JF, Matsuzaki Y, Jiang QJ, et al. Targeted ablation of the Abcc6 gene results in ectopic mineralization of connective tissues. Mol Cell Biol 2005;25:8299-310
  • Gorgels TG, Hu X, Scheffer GL, et al. Disruption of Abcc6 in the mouse: novel insight in the pathogenesis of pseudoxanthoma elasticum. Hum Mol Genet 2005;14:1763-73
  • LaRusso J, Li Q, Jiang Q, et al. Elevated dietary magnesium prevents connective tissue mineralization in a mouse model of pseudoxanthoma elasticum (Abcc6-/-). J Invest Dermatol 2009;129:1388-94
  • Gorgels TG, Waarsing JH, de Wolf A, et al. Dietary magnesium, not calcium, prevents vascular calcification in a mouse model for pseudoxanthoma elasticum. J Mol Med (Berl) 2010;88:467-75
  • Jiang Q, Uitto J. Restricting dietary magnesium accelerates ectopic connective tissue mineralization in a mouse model of pseudoxanthoma elasticum (Abcc6-/-). Exp Dermatol 2012;21:694-9
  • Sherer DW, Singer G, Uribarri J, et al. Oral phosphate binders in the treatment of pseudoxanthoma elasticum. J Am Acad Dermatol 2005;53:610-15
  • Yoo JY, Blum RR, Singer GK, et al. A randomized controlled trial of oral phosphate binders in the treatment of pseudoxanthoma elasticum. J Am Acad Dermatol 2011;65:341-8
  • Otero JE, Gottesman GS, McAlister WH, et al. Severe skeletal toxicity from protracted etidronate therapy for generalized arterial calcification of infancy. J Bone Miner Res 2013;28:419-30
  • Edouard T, Chabot G, Miro J, et al. Efficacy and safety of 2-year etidronate treatment in a child with generalized arterial calcification of infancy. Eur J Pediatr 2011;170:1585-90
  • Jansen RS, Kucukosmanoglu A, de Haas M, et al. ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci USA 2013;110:20206-11
  • Boraldi F, Annovi G, Bartolomeo A, et al. Fibroblasts from patients affected by Pseudoxanthoma elasticum exhibit an altered PPi metabolism and are more responsive to pro-calcifying stimuli. J Dermatol Sci 2014;74:72-80
  • Jahnen-Dechent W, Schinke T, Trindl A, et al. Cloning and targeted deletion of the mouse fetuin gene. J Biol Chem 1997;272:31496-503
  • Jiang Q, Dibra F, Lee MD, et al. Overexpression of fetuin-a counteracts ectopic mineralization in a mouse model of pseudoxanthoma elasticum (abcc6-/-). J Invest Dermatol 2010;130:1288-96
  • Zhou Y, Jiang Q, Takahagi S, et al. Premature termination codon read-through in the ABCC6 gene: potential treatment for pseudoxanthoma elasticum. J Invest Dermatol 2013;133:2672-7
  • Le Saux O, Fülop K, Yamaguchi Y, et al. Expression and in vivo rescue of human ABCC6 disease-causing mutants in mouse liver. PLoS One 2011;6:e24738
  • Jiang Q, Takahagi S, Uitto J. Administration of bone marrow derived mesenchymal stem cells into the liver: Potential to rescue pseudoxanthoma elasticum in a mouse model (Abcc6-/-). J Biomed Biotech 2012;2012:818937
  • Gaestel A. A Philadelphia meeting talks treatment for a rare disease. The Philadelphia Inquirer 2012. Available from: http://articles.philly.2012-07-15/news/32675524_1_rare-diseases-mutant-protein-nih
  • Brewer GJ. Drug development for orphan diseases in the context of personalized medicine. Transl Res 2009;154:314-22
  • Li Q, Uitto J. The mineralization phenotype in Abcc6 (-/-) mice is affected by Ggcx gene deficiency and genetic background--a model for pseudoxanthoma elasticum. J Mol Med (Berl) 2010;88:173-81
  • Li Q, Guo H, Chou DW, et al. Mouse models for pseudoxanthoma elasticum: genetic and dietary modulation of the ectopic mineralization phenotypes. PLoS One 2013;9:e89268
  • Sardana D, Zhu C, Zhang M, et al. Drug repositioning for orphan diseases. Brief Bioinform 2011;12:346-56
  • Guo H, Li Q, Chou DW, et al. Atorvastatin counteracts aberrant soft tissue mineralization in a mouse model of pseudoxanthoma elasticum (Abcc6-/-). J Mol Med (Berl) 2013;91:1177-84
  • Li Q, Baker J, Kowalczyk J, et al. Pediatric pseudoxanthoma elasticum with cardiovascular involvement. Br J Dermatol 2013;169:1148-51

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.