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Pseudoxanthoma elasticum

Reviewed January 2015

What is pseudoxanthoma elasticum?

Pseudoxanthoma elasticum (PXE) is a progressive disorder that is characterized by the accumulation of deposits of calcium and other minerals (mineralization) in elastic fibers. Elastic fibers are a component of connective tissue, which provides strength and flexibility to structures throughout the body.

In PXE, mineralization can affect elastic fibers in the skin, eyes, and blood vessels, and less frequently in other areas such as the digestive tract. People with PXE may have yellowish bumps called papules on their necks, underarms, and other areas of skin that touch when a joint bends (flexor areas). They may also have abnormalities in the eyes, such as a change in the pigmented cells of the retina (the light-sensitive layer of cells at the back of the eye) known as peau d'orange. Another eye abnormality known as angioid streaks occurs when tiny breaks form in the layer of tissue under the retina called Bruch's membrane. Bleeding and scarring of the retina may also occur, which can cause vision loss.

Mineralization of the blood vessels that carry blood from the heart to the rest of the body (arteries) may cause other signs and symptoms of PXE. For example, people with this condition can develop narrowing of the arteries (arteriosclerosis) or a condition called claudication that is characterized by cramping and pain during exercise due to decreased blood flow to the arms and legs. Rarely, bleeding from blood vessels in the digestive tract may also occur.

How common is pseudoxanthoma elasticum?

PXE affects approximately 1 in 50,000 people worldwide. For reasons that are unclear, this disorder is diagnosed twice as frequently in females as in males.

What genes are related to pseudoxanthoma elasticum?

Mutations in the ABCC6 gene cause PXE. This gene provides instructions for making a protein called MRP6 (also known as the ABCC6 protein). This protein is found primarily in cells of the liver and kidneys, with small amounts in other tissues, including the skin, stomach, blood vessels, and eyes. MRP6 is thought to transport certain substances across the cell membrane; however, the substances have not been identified. Some studies suggest that the MRP6 protein stimulates the release of a molecule called adenosine triphosphate (ATP) from cells through an unknown mechanism. ATP can be broken down into other molecules, including adenosine monophosphate (AMP) and pyrophosphate. Pyrophosphate helps control deposition of calcium and other minerals in the body. Other studies suggest that a substance transported by MRP6 is involved in the breakdown of ATP. This unidentified substance is thought to help prevent mineralization of tissues.

Mutations in the ABCC6 gene lead to an absent or nonfunctional MRP6 protein. It is unclear how a lack of properly functioning MRP6 protein leads to PXE. This shortage may impair the release of ATP from cells. As a result, little pyrophosphate is produced, and calcium and other minerals accumulate in elastic fibers of the skin, eyes, blood vessels and other tissues affected by PXE. Alternatively, a lack of functioning MRP6 may impair the transport of a substance that would normally prevent mineralization, leading to the abnormal accumulation of calcium and other minerals characteristic of PXE.

Related Gene(s)

Changes in this gene are associated with pseudoxanthoma elasticum.

  • ABCC6

How do people inherit pseudoxanthoma elasticum?

PXE is inherited in an autosomal recessive manner, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

In a few cases, an affected individual has one affected parent and one parent without the signs and symptoms of the disorder. This situation resembles autosomal dominant inheritance, in which one copy of an altered gene in each cell is sufficient to cause a disorder and the mutation is typically inherited from one affected parent. In these cases of PXE, however, the parent without apparent symptoms has an ABCC6 gene mutation. The affected offspring inherits two altered genes, one from each parent. This appearance of autosomal dominant inheritance when the pattern is actually autosomal recessive is called pseudodominance.

Where can I find information about diagnosis or management of pseudoxanthoma elasticum?

These resources address the diagnosis or management of pseudoxanthoma elasticum and may include treatment providers.

  • Gene Review: Pseudoxanthoma Elasticum (http://www.ncbi.nlm.nih.gov/books/NBK1113)
  • Genetic Testing Registry: Pseudoxanthoma elasticum (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0033847)

You might also find information on the diagnosis or management of pseudoxanthoma elasticum in Educational resources (/condition/pseudoxanthoma-elasticum/show/Educational+resources) and Patient support (/condition/pseudoxanthoma-elasticum/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about pseudoxanthoma elasticum?

You may find the following resources about pseudoxanthoma elasticum helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for pseudoxanthoma elasticum?

  • Groenblad-Strandberg syndrome
  • Gronblad-Strandberg syndrome
  • PXE

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about pseudoxanthoma elasticum?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding pseudoxanthoma elasticum?

adenosine triphosphate ; angioid streaks ; arteries ; arteriosclerosis ; ATP ; autosomal ; autosomal dominant ; autosomal recessive ; breakdown ; calcium ; cell ; cell membrane ; claudication ; connective tissue ; digestive ; elastic ; gene ; inheritance ; inherited ; joint ; molecule ; mutation ; offspring ; protein ; pseudodominance ; recessive ; retina ; stomach ; syndrome ; tissue

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (/glossary).

References

  • Bercovitch L, Terry P. Pseudoxanthoma elasticum 2004. J Am Acad Dermatol. 2004 Jul;51(1 Suppl):S13-4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15243491?dopt=Abstract)
  • Chassaing N, Martin L, Calvas P, Le Bert M, Hovnanian A. Pseudoxanthoma elasticum: a clinical, pathophysiological and genetic update including 11 novel ABCC6 mutations. J Med Genet. 2005 Dec;42(12):881-92. Epub 2005 May 13. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15894595?dopt=Abstract)
  • Dabisch-Ruthe M, Kuzaj P, Götting C, Knabbe C, Hendig D. Pyrophosphates as a major inhibitor of matrix calcification in Pseudoxanthoma elasticum. J Dermatol Sci. 2014 Aug;75(2):109-20. doi: 10.1016/j.jdermsci.2014.04.015. Epub 2014 May 17. (http://www.ncbi.nlm.nih.gov/pubmed/24907773?dopt=Abstract)
  • Gene Review: Pseudoxanthoma Elasticum (http://www.ncbi.nlm.nih.gov/books/NBK1113)
  • Hu X, Plomp A, Wijnholds J, Ten Brink J, van Soest S, van den Born LI, Leys A, Peek R, de Jong PT, Bergen AA. ABCC6/MRP6 mutations: further insight into the molecular pathology of pseudoxanthoma elasticum. Eur J Hum Genet. 2003 Mar;11(3):215-24. (http://www.ncbi.nlm.nih.gov/pubmed/12673275?dopt=Abstract)
  • Jansen RS, Duijst S, Mahakena S, Sommer D, Szeri F, Váradi A, Plomp A, Bergen AA, Oude Elferink RP, Borst P, van de Wetering K. ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report. Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):1985-9. doi: 10.1161/ATVBAHA.114.304017. Epub 2014 Jun 26. (http://www.ncbi.nlm.nih.gov/pubmed/24969777?dopt=Abstract)
  • Jansen RS, Küçükosmanoglu A, de Haas M, Sapthu S, Otero JA, Hegman IE, Bergen AA, Gorgels TG, Borst P, van de Wetering K. ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20206-11. doi: 10.1073/pnas.1319582110. Epub 2013 Nov 25. (http://www.ncbi.nlm.nih.gov/pubmed/24277820?dopt=Abstract)
  • Laube S, Moss C. Pseudoxanthoma elasticum. Arch Dis Child. 2005 Jul;90(7):754-6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15970621?dopt=Abstract)
  • Le Saux O, Beck K, Sachsinger C, Silvestri C, Treiber C, Göring HH, Johnson EW, De Paepe A, Pope FM, Pasquali-Ronchetti I, Bercovitch L, Marais AS, Viljoen DL, Terry SF, Boyd CD. A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum. Am J Hum Genet. 2001 Oct;69(4):749-64. Epub 2001 Aug 31. Erratum in: Am J Hum Genet 2002 Aug;71(2):448. Am J Hum Genet 2001 Dec;69(6):1413. (http://www.ncbi.nlm.nih.gov/pubmed/11536079?dopt=Abstract)
  • Miksch S, Lumsden A, Guenther UP, Foernzler D, Christen-Zäch S, Daugherty C, Ramesar RK, Lebwohl M, Hohl D, Neldner KH, Lindpaintner K, Richards RI, Struk B. Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6. Hum Mutat. 2005 Sep;26(3):235-48. (http://www.ncbi.nlm.nih.gov/pubmed/16086317?dopt=Abstract)
  • Plomp AS, Hu X, de Jong PT, Bergen AA. Does autosomal dominant pseudoxanthoma elasticum exist? Am J Med Genet A. 2004 May 1;126A(4):403-12. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15098239?dopt=Abstract)
  • Ringpfeil F, McGuigan K, Fuchsel L, Kozic H, Larralde M, Lebwohl M, Uitto J. Pseudoxanthoma elasticum is a recessive disease characterized by compound heterozygosity. J Invest Dermatol. 2006 Apr;126(4):782-6. (http://www.ncbi.nlm.nih.gov/pubmed/16410789?dopt=Abstract)
  • Ringpfeil F, Pulkkinen L, Uitto J. Molecular genetics of pseudoxanthoma elasticum. Exp Dermatol. 2001 Aug;10(4):221-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11493310?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: January 2015
Published: May 4, 2015