2,090 results match your criteria Pseudoxanthoma Elasticum


The Impact of Inflammatory Stimuli on Xylosyltransferase-I Regulation in Primary Human Dermal Fibroblasts.

Biomedicines 2022 Jun 19;10(6). Epub 2022 Jun 19.

Institut für Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum NRW, Universitätsklinik der Ruhr-Universität Bochum, Georgstraße 11, 32545 Bad Oeynhausen, Germany.

Inflammation plays a vital role in regulating fibrotic processes. Beside their classical role in extracellular matrix synthesis and remodeling, fibroblasts act as immune sentinel cells participating in regulating immune responses. The human xylosyltransferase-I (XT-I) catalyzes the initial step in proteoglycan biosynthesis and was shown to be upregulated in normal human dermal fibroblasts (NHDF) under fibrotic conditions. Read More

View Article and Full-Text PDF

A case of angioid streaks that produced choroidal neovascularization after the onset of unilateral acute retinopathy in pseudoxanthoma elasticum.

Am J Ophthalmol Case Rep 2022 Sep 19;27:101591. Epub 2022 May 19.

Department of Ophthalmology and Visual Sciences, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.

Purpose: To report a case of angioid streaks that showed non-exudative choroidal neovascularization (CNV) after the onset of acute retinopathy in pseudoxanthoma elasticum (PXE).

Observations: A 64-year-old woman with PXE visited our department for an ophthalmologic evaluation. Her decimal best-corrected visual acuity (BCVA) was 1. Read More

View Article and Full-Text PDF
September 2022

Vitamin K-Dependent Protein Activation: Normal Gamma-Glutamyl Carboxylation and Disruption in Disease.

Int J Mol Sci 2022 May 20;23(10). Epub 2022 May 20.

Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine at CWRU, Cleveland, OH 44195, USA.

Vitamin K-dependent (VKD) proteins undergo an unusual post-translational modification, which is the conversion of specific Glu residues to carboxylated Glu (Gla). Gla generation is required for the activation of VKD proteins, and occurs in the endoplasmic reticulum during their secretion to either the cell surface or from the cell. The gamma-glutamyl carboxylase produces Gla using reduced vitamin K, which becomes oxygenated to vitamin K epoxide. Read More

View Article and Full-Text PDF

Relationships between Plasma Pyrophosphate, Vascular Calcification and Clinical Severity in Patients Affected by Pseudoxanthoma Elasticum.

J Clin Med 2022 May 5;11(9). Epub 2022 May 5.

PXE Reference Center, MAGEC Nord, University Hospital of Angers, 49000 Angers, France.

Pseudoxanthoma elasticum (PXE; OMIM 264800) is an autosomal recessive metabolic disorder characterized by progressive calcification in the skin, the Bruch's membrane, and the vasculature. Calcification in PXE results from a low level of circulating pyrophosphate (PPi) caused by ABCC6 deficiency. In this study, we used a cohort of 107 PXE patients to determine the pathophysiological relationship between plasma PPi, coronary calcification (CAC), lower limbs arterial calcification (LLAC), and disease severity. Read More

View Article and Full-Text PDF

Various vascular malformations are prevalent in Finnish pseudoxanthoma elasticum (PXE) patients: a national registry study.

Orphanet J Rare Dis 2022 05 7;17(1):185. Epub 2022 May 7.

Department of Internal Medicine, Tampere University Hospital, Teiskontie 35, 33521, Tampere, Finland.

Background: Pseudoxanthoma elasticum (PXE, OMIM# 264800) is an inborn error of metabolism causing ectopic soft tissue calcification due to low plasma pyrophosphate concentration. We aimed to assess the prevalence of PXE in Finland and to characterize the Finnish PXE population. A nationwide registry search was performed to identify patients with ICD-10 code Q82. Read More

View Article and Full-Text PDF

INZ-701, a recombinant ENPP1 enzyme, prevents ectopic calcification in an Abcc6 mouse model of pseudoxanthoma elasticum.

Exp Dermatol 2022 May 5. Epub 2022 May 5.

Inozyme Pharma, Boston, Massachusetts, USA.

Pseudoxanthoma elasticum (PXE), a heritable multisystem ectopic calcification disorder, is predominantly caused by inactivating mutations in ABCC6. The encoded protein, ABCC6, is a hepatic efflux transporter and a key regulator of extracellular inorganic pyrophosphate (PPi). Recent studies demonstrated that deficiency of plasma PPi, a potent endogenous calcification inhibitor, is the underlying cause of PXE. Read More

View Article and Full-Text PDF

Pseudoxanthoma elasticumban szenvedő betegek multidiszciplináris ellátása.

Orv Hetil 2022 May 1;163(18):702-711. Epub 2022 May 1.

1 Semmelweis Egyetem, Általános Orvostudományi Kar, Bőr-, Nemikórtani és Bőronkológiai Klinika Budapest, Mária u. 41., 1085 Magyarország.

Összefoglaló. A pseudoxanthoma elasticum (PXE, OMIM # 264800) egy autoszomális recesszív módon öröklődő multiszisztémás érintettséggel járó kórkép, melynek háttérében az ABCC6 gén mutációi állnak. A tünetek kialakulásának oka az ektópiás mineralizáció. Read More

View Article and Full-Text PDF

ENPP1 variants in patients with GACI and PXE expand the clinical and genetic heterogeneity of heritable disorders of ectopic calcification.

PLoS Genet 2022 04 28;18(4):e1010192. Epub 2022 Apr 28.

Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.

Pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI) are clinically distinct genetic entities of ectopic calcification associated with differentially reduced circulating levels of inorganic pyrophosphate (PPi), a potent endogenous inhibitor of calcification. Variants in ENPP1, the gene mutated in GACI, have not been associated with classic PXE. Here we report the clinical, laboratory, and molecular evaluations of ten GACI and two PXE patients from five and two unrelated families registered in GACI Global and PXE International databases, respectively. Read More

View Article and Full-Text PDF

Mutation update: Variants of the ENPP1 gene in pathologic calcification, hypophosphatemic rickets, and cutaneous hypopigmentation with punctate keratoderma.

Hum Mutat 2022 Apr 27. Epub 2022 Apr 27.

Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

ENPP1 encodes ENPP1, an ectonucleotidase catalyzing hydrolysis of ATP to AMP and inorganic pyrophosphate (PPi), and an endogenous plasma protein physiologically preventing ectopic calcification of connective tissues. Mutations in ENPP1 have been reported in association with a range of human genetic diseases. In this mutation update, we provide a comprehensive review of all the pathogenic variants, likely pathogenic variants, and variants of unknown significance in ENPP1 associated with three autosomal recessive disorders-generalized arterial calcification of infancy (GACI), autosomal recessive hypophosphatemic rickets type 2 (ARHR2), and pseudoxanthoma elasticum (PXE), as well as with a predominantly autosomal dominant disorder-Cole disease. Read More

View Article and Full-Text PDF

Pseudoxanthoma elasticum causing extensive myocardial calcification.

Eur Heart J Case Rep 2022 Apr 30;6(4):ytac141. Epub 2022 Mar 30.

Morriston Hospital, Swansea Bay University Health Board, Swansea SA6 6NL, UK.

View Article and Full-Text PDF

Intracranial atherosclerosis in pseudoxanthoma elasticum: A case-control study.

Atherosclerosis 2022 06 15;350:19-24. Epub 2022 Apr 15.

Department of Radiology, University Medical Center Utrecht and Utrecht University, Utrecht, the Netherlands. Electronic address:

Background And Aims: Pseudoxanthoma elasticum (PXE) is a genetic disorder characterized by systemic calcification of elastin fibers. Additionally, PXE is associated with an increased risk of stroke. It has been hypothesized that this may be caused by accelerated (intracranial) atherogenesis, as a consequence of specific genetic mutations underlying PXE. Read More

View Article and Full-Text PDF

Pseudoxanthoma elasticum as a diagnostic challenge for pathologists: A rare case report.

Ann Med Surg (Lond) 2022 May 3;77:103571. Epub 2022 Apr 3.

Deptt. of Pathology, North DMC, Medical College, Hindu Rao Hospital, Delhi, India.

•PXE is an extremely rare autosomal recessive disease.•It involves major systems in the body like the cutaneous, ocular, cardiovascular, and gastrointestinal.•The characteristic histopathological features are calcification and fragmentation of the elastic fibres. Read More

View Article and Full-Text PDF

The Relevance of Skin Biopsies in General Internal Medicine: Facts and Myths.

Dermatol Ther (Heidelb) 2022 May 17;12(5):1103-1119. Epub 2022 Apr 17.

Department of Dermatology, University Hospital Centre, CHU du Sart Tilman, University of Liège, 4000, Liège, Belgium.

Introduction: Non-dermatology medical specialties may refer patients for skin biopsies, searching for a particular diagnosis. However, the diagnostic impact of the skin biopsy is not clearly established. This article aims to assess the indications for, and evaluate the clinical relevance of, skin biopsies in non-dermatology medical specialties. Read More

View Article and Full-Text PDF

[Pseudoxanthoma elasticum: the dermatologist as a guide].

Hautarzt 2022 Apr 15. Epub 2022 Apr 15.

Abteilung für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Deutschland.

Characteristic skin changes lead to diagnosis of pseudoxanthoma elasticum (PXE), an ectopic mineralization disorder, involving primarily the skin, eyesight, and arterial vessels. Early recognition is crucial for timely treatment of extracutaneous complications. We hereby report a series of four cases of PXE with pathognomonic skin lesions and a broad spectrum of systemic complications. Read More

View Article and Full-Text PDF

Author reply to comment on "Clinical practice guidelines for pseudoxanthoma elasticum (2017)": The importance of mutation analysis.

J Dermatol 2022 Apr 8. Epub 2022 Apr 8.

Graduate School of Biomedical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University - Dermatology, Nagasaki, Japan.

View Article and Full-Text PDF

Cutaneous vascular calcification. Perieccrine calcification as a diagnostic key for calciphylaxis.

J Cutan Pathol 2022 Mar 31. Epub 2022 Mar 31.

Dermatology Department, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-IP), Madrid, Spain.

Background: Attempts have been made to establish discriminative criteria between classic calciphylaxis (CPX) and those cases in which cutaneous vascular calcification (CVC) represents an incidental finding (epiphenomenon).

Methods: Retrospective, observational cohort study of patients with CVC to distinguish clinicopathological features between CVC as classic CPX (CVC in cutaneous lesions with erythematous-violaceous plaques with or without ulceration) or as an epiphenomenon (CVC in cutaneous lesions with known diagnosis). Different clinicopathological parameters and the presence of perieccrine calcification and pseudoxanthoma elasticum (PXE)-like changes were evaluated. Read More

View Article and Full-Text PDF

Commentary on Variants in the ABCC6 Gene Implicated in Pseudoxanthoma Elasticum, a Heritable Ectopic Mineralization Disorder.

J Invest Dermatol 2022 04;142(4):1002-1003

Department of Microbiology & Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Electronic address:

Significant progress has been made in understanding pseudoxanthoma elasticum (PXE), which results from mutations in ABCC6. The low prevalence of PXE and its heterotypic presentation confound genotype-phenotype correlations and the characterization of many identified variants. Kowal et al. Read More

View Article and Full-Text PDF

Comment on "Clinical practice guidelines for pseudoxanthoma elasticum (2017)": The importance of mutation analysis.

J Dermatol 2022 Mar 22. Epub 2022 Mar 22.

Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

View Article and Full-Text PDF

The Abcc6a Knockout Zebrafish Model as a Novel Tool for Drug Screening for Pseudoxanthoma Elasticum.

Front Pharmacol 2022 4;13:822143. Epub 2022 Mar 4.

Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.

Pseudoxanthoma elasticum (PXE) is a multisystem ectopic mineralization disorder caused by pathogenic variants in the ABCC6 gene. Though complications of the disease can be treated, PXE itself remains currently intractable. A strategy for rapid and cost-effective discovery of therapeutic drugs would be to perform chemical compound screening using zebrafish, but this approach remains to be validated for PXE. Read More

View Article and Full-Text PDF

Healthcare transition from childhood to adulthood in pseudoxanthoma elasticum: Patient experience and recommendations for health practitioners.

Ann Dermatol Venereol 2022 Mar 17. Epub 2022 Mar 17.

Dermatology Department, Reference Centre for Pseudoxanthoma Elasticum (MAGEC), Angers University Hospital, 4, rue Larrey, 49933 Angers, France.

Purpose: Health-care transition (HCT) is a necessary part of the care process for allsick adolescents, to allow their empowerment while limiting disruption to follow-up care. Pseudoxanthoma elasticum (PXE) runs the risk of losing patients to follow-up because young patients are predominantly asymptomatic. This can be detrimental as it can prevent primary prevention measures from being properly implemented. Read More

View Article and Full-Text PDF

Pulmonary affection of patients with Pseudoxanthoma elasticum: Long-term development and genotype-phenotype-correlation.

Intractable Rare Dis Res 2022 Feb;11(1):7-14

Department of Internal Medicine II, Cardiology, Pneumology and Angiology, University Hospital Bonn, Bonn, Germany.

Pseudoxanthoma elasticum (PXE) is a rare, heritable disease caused by various, mainly recessively transmitted mutations in the gene. Due to calcification of soft connective tissue phenotypic hallmarks are progressive loss of vision, alternation of the skin and early onset atherosclerosis. Beside these main features patients also suffer from impaired alveolar diffusion. Read More

View Article and Full-Text PDF
February 2022

Vitamin D and Calcium Supplementation Accelerate Vascular Calcification in a Model of Pseudoxanthoma Elasticum.

Int J Mol Sci 2022 Feb 19;23(4). Epub 2022 Feb 19.

UMR S 1155, Sorbonne Université, 75020 Paris, France.

Arterial calcification is a common feature of pseudoxanthoma elasticum (PXE), a disease characterized by mutations, inducing a deficiency in pyrophosphate, a key inhibitor of calcium phosphate crystallization in arteries.

Methods: we analyzed whether long-term exposure of Abcc6 mice (a murine model of PXE) to a mild vitamin D supplementation, with or without calcium, would impact the development of vascular calcification. Eight groups of mice (including Abcc6 and wild-type) received vitamin D supplementation every 2 weeks, a calcium-enriched diet alone (calcium in drinking water), both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Read More

View Article and Full-Text PDF
February 2022

Progressive Dermopathy akin to Pseudoxanthoma Elasticum after D-penicillamine Use in a Patient with Cystinuria.

Rheumatology (Oxford) 2022 Feb 25. Epub 2022 Feb 25.

Department of Rheumatology, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, UK.

View Article and Full-Text PDF
February 2022

Pigmentary Retinopathy and Chronic Subretinal Fluid Associated with Pseudoxanthoma Elasticum and Angioid Streaks.

J Ophthalmic Vis Res 2022 Jan-Mar;17(1):152-155. Epub 2022 Jan 21.

Mayo Clinic Department of Ophthalmology, Rochester, MN, USA.

View Article and Full-Text PDF
January 2022

Null Mice-a Model for Mineralization Disorder PXE Shows Vertebral Osteopenia Without Enhanced Intervertebral Disc Calcification With Aging.

Front Cell Dev Biol 2022 3;10:823249. Epub 2022 Feb 3.

Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, PA, United States.

Chronic low back pain is a highly prevalent health condition intricately linked to intervertebral disc degeneration. One of the prominent features of disc degeneration that is commonly observed with aging is dystrophic calcification. ATP-binding cassette sub-family C member 6 (ABCC6), a presumed ATP efflux transporter, is a key regulator of systemic levels of the mineralization inhibitor pyrophosphate (PPi). Read More

View Article and Full-Text PDF
February 2022

Inorganic Pyrophosphate Deficiency Syndromes and Potential Treatments for Pathologic Tissue Calcification.

Am J Pathol 2022 05 16;192(5):762-770. Epub 2022 Feb 16.

Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Jefferson Institute of Molecular Medicine, and the PXE International Center of Excellence in Research and Clinical Care, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address:

Pathologic soft tissue calcification can occur in both genetic and acquired clinical conditions, causing significant morbidity and mortality. Although the pathomechanisms of pathologic calcification are poorly understood, major progress has been made in recent years in defining the underlying genetic defects in Mendelian disorders of ectopic calcification. This review presents an overview of the pathophysiology of five monogenic disorders of pathologic calcification: pseudoxanthoma elasticum, generalized arterial calcification of infancy, arterial calcification due to deficiency of CD73, ankylosis, and progeria. Read More

View Article and Full-Text PDF

Minocycline Counteracts Ectopic Calcification in a Murine Model of Pseudoxanthoma Elasticum: A Proof-of-Concept Study.

Int J Mol Sci 2022 Feb 6;23(3). Epub 2022 Feb 6.

Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium.

Pseudoxanthoma elasticum (PXE) is an intractable Mendelian disease characterized by ectopic calcification in skin, eyes and blood vessels. Recently, increased activation of the DNA damage response (DDR) was shown to be involved in PXE pathogenesis, while the DDR/PARP1 inhibitor minocycline was found to attenuate aberrant mineralization in PXE cells and zebrafish. In this proof-of-concept study, we evaluated the anticalcifying properties of minocycline in mice, an established mammalian PXE model. Read More

View Article and Full-Text PDF
February 2022

Low concentration staining for high chemical contrast, nonlinear microscope mosaic imaging of skin alterations in pseudoxanthoma elasticum.

Biomed Opt Express 2022 Jan 8;13(1):252-261. Epub 2021 Dec 8.

Wigner RCP, Institute for Solid State Physics and Optics, P.O. Box 49, H-1525 Budapest, Hungary.

Pseudoxanthoma elasticum (PXE) is an autosomal recessive metabolic disorder characterized by ectopic mineralization of soft connective tissue. Histopathology findings include fragmented, mineralized elastic fibers and calcium deposits in the mid-dermis. Nonlinear microscopy (NLM) can be used for visualization of these histopathological alterations of the mid-dermis in PXE-affected skin sections. Read More

View Article and Full-Text PDF
January 2022

Inhibition of the DNA Damage Response Attenuates Ectopic Calcification in Pseudoxanthoma Elasticum.

J Invest Dermatol 2022 Feb 7. Epub 2022 Feb 7.

Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Department of Dermatology & Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; PXE International Center of Excellence in Research and Clinical Care, Department of Dermatology & Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Electronic address:

Pseudoxanthoma elasticum (PXE) is a heritable ectopic calcification disorder with multiorgan clinical manifestations. The gene at default, ABCC6, encodes an efflux transporter, ABCC6, which is a critical player regulating the homeostasis of inorganic pyrophosphate, a potent endogenous anticalcification factor. Previous studies suggested that systemic inorganic pyrophosphate deficiency is the major but not the exclusive cause of ectopic calcification in PXE. Read More

View Article and Full-Text PDF
February 2022