title: Pseudoxanthoma elasticum, the paradigm of heritable ectopic mineralization disorders - can diet help?
abstract: Pseudoxanthoma elasticum (PXE) is a heritable multi-system disorder manifesting with characteristic cutaneous lesions, associated with ocular findings and cardiovascular involvement. The skin lesions, yellowish papules which coalesce into plaques of inelastic and leathery skin, demonstrate by histopathologic and ultrastructural examinations ectopic mineralization of dermal connective tissues, primarily the elastic structures. PXE is inherited in an autosomal recessive fashion due to mutations in the ABCC6 gene. Significant insights into the pathogenesis of PXE have been recently obtained from observations on the Abcc6(-/-) knockout mouse which mimics the genetic, histopathologic and ultrastructural features of PXE. This mouse model has provided a platform to test various treatment modalities to counteract the mineralization phenotypes. One of the intriguing findings emanating from these studies is that supplementation of the mouse diet with magnesium, at levels that are ∼5-fold higher than those in control diet, completely inhibits the development of tissue mineralization. These and related observations suggest that changes in the diet might counteract the progression of PXE and improve the quality of life of patients with this, currently intractable, disease.
authors: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, USA.
authors: Jennifer
authors: J
authors: LaRusso
authors: Qiaoli
authors: Q
authors: Li
authors: Jouni
authors: J
authors: Uitto
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005808:Genes, Recessive / Q000235:genetics; D006801:Humans; D008274:Magnesium / Q000008:administration & dosage*; D051379:Mice; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D010641:Phenotype; D011561:Pseudoxanthoma Elasticum / Q000175:diagnosis / Q000178:diet therapy* / Q000235:genetics; D011788:Quality of Life
chemical_list: D018528:ATP-Binding Cassette Transporters; D008274:Magnesium; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human; C504743:Abcc6 protein, mouse