PXE and the Metabolism

The connection between PXE and the metabolism has been the topic of interest for many PXE researchers for many years. Multiple research avenues have been pursued to attempt to elucidate the complex nature of the pathology associated with PXE manifestations. However, studies with the Abcc6 knockout mouse provided the definite evidence that PXE is a metabolic disease.

Two experiments were performed using multiple combinations involving the transfer of vibrissae skin between KO and wild type mice to examine the possibility of a serum factor being the cause of the tissue mineralization seen in PXE. The team found that the WT skin on the back of the KO mouse, which was not mineralized at the start, became mineralized in 28.6% of the mice after it was grafted on the skin of the KO mice, while the KO skin was not mineralized at all after it was grafted on to the WT mouse´s back. In the second study the grafts were performed at 12 weeks of age after the muzzle skin of the KO mouse already showed mineralization. Researchers found that the KO skin grafted on to the WT mouse was less mineralized than it was at the time of grafting, and the KO skin grafted onto the KO mouse was more than twice as mineralized as it was at the time of grafting. These experiments demonstrate that a metabolite circulating the in bloodstream of affected individuals results in the clinical manifestations seen in PXE.

Currently, research is continuing to identify the serum factor involved in PXE. Studies are also underway to examine the effects of various dietary modifications on the development and severity of PXE, including phosphate, vitamin K, calcium, and magnesium.

Primary Researchers

Lionel Bercovitch
Piet Borst
Michael Dean
Anne De Paepe
Timothy Hefferon
Doris Hendig
Robert Jansen
Qiujie Jiang
Olivier Le Saux
Qiaoli Li
Ludovic Martin
Ivonne Pasquali-Ronchetti
Daniela Quaglino
Jouni Uitto
Olivier Vanakker
Koen van de Wetering
András Váradi

Related Articles

Fülöp K, Jiang Q, Wetering KV, Pomozi V, Szabó PT, Arányi T, Sarkadi B, Borst P, Uitto J, Váradi A. ABCC6 does not transport vitamin K3-glutathione conjugate from the liver: relevance to pathomechanisms of pseudoxanthoma elasticum. Biochem Biophys Res Commun. 2011 Nov 25;415(3):468-71. PMID: 22056557

Vasseur M, Carsin-Nicol B, Ebran Jm, Willoteaux S, Martin LLefthériotis G, on the behalf of the Angers PXE Consultation Center Group. Carotid rete mirabile and pseudoxanthoma elasticum: An accidental association? Eur J Vasc Endovasc Surg. 2011 Sep;42(3):292-4. PMID: 21723754

Yoo JY, Blum RR, Singer GK, Stern DK, Emanuel PO, Fuchs W, Phelps RG, Terry SF, Lebwohl MG. A randomized controlled trial of oral phosphate binders in the treatment of pseudoxanthoma elasticum. J Am Acad Dermatol. 2011 Aug;65(2):341-8. PMID: 21496949

Larusso J, Li Q, Uitto J. Pseudoxanthoma elasticum, the paradigm of heritable ectopic mineralization disorders - Can diet help? J Dtsch Dermatol Ges. 2011 Aug;9(8):586-93. Free article in PubMed. PMID: 21435181

Jiang Q, Endo M, Dibra F, Wang K, Uitto J. Pseudoxanthoma elasticum is a metabolic disease. J Invest Dermatol. 2009 Feb;129(2):348-54. Patient Summary. Free article in PubMed. PMID: 18685618

Garcia-Fernandez MI, Gheduzzi D, Boraldi F, Paolinelli CD, Sanchez P, Valdivielso P, Morilla MJ, Quaglino D, Guerra D, Casolari S, Bercovitch LPasquali-Ronchetti I. Parameters of oxidative stress are present in the circulation of PXE patients. Biochim Biophys Acta. 2008 Jul-Aug;1782(7-8):474-81. PMID: 18513494

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 Jun 1;7(11):1575-9. Free article at Journal Website. PMID: 18469514

Jiang QUitto J. Pseudoxanthoma elasticum: a metabolic disease? J Invest Dermatol. 2006 Jul;126(7):1440-1. Free article at Journal Website. PMID: 16778810

Le Saux O, Bunda S, VanWart CM, Douet V, Got L, Martin L, Hinek A. Serum factors from pseudoxanthoma elasticum patients alter elastic fiber formation in vitro. J Invest Dermatol. 2006 Jul;126(7):1497-505. Free article at Journal Website. PMID: 16543900

Hendig D, Schulz V, Arndt M, Szliska C, Kleesiek K, Götting C. Role of serum fetuin-A, a major inhibitor of systemic calcification, in pseudoxanthoma elasticum. Clin Chem. 2006 Feb;52(2):227-34. Free article at Journal Website. PMID: 16384891

Pasquali-Ronchetti I, Garcia-Fernandez MI, Boraldi F, Quaglino D, Gheduzzi D, De Vincenzi Paolinelli C, Tiozzo R, Bergamini S, Ceccarelli D, Muscatello U. Oxidative stress in fibroblasts from patients with pseudoxanthoma elasticum: possible role in the pathogenesis of clinical manifestations. J Pathol. 2006 Jan;208(1):54-61. PMID: 16261549

Annovazzi L, Viglio S, Gheduzzi D, Pasquali-Ronchetti I, Zanone C, Cetta G, Iadarola P. High levels of desmosines in urine and plasma of patients with pseudoxanthoma elasticum. Eur J Clin Invest. 2004 Feb;34(2):156-64. PMID: 14764080

Uitto J, Pulkkinen L, Ringpfeil F. Molecular genetics of pseudoxanthoma elasticum: a metabolic disorder at the environment-genome interface? Trends Mol Med. 2001 Jan;7(1):13-7. PMID: 11427982