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Clinical & Experimental Optometry Mar 2011Pseudoxanthoma elasticum (PXE), also known as Groenblad syndrome, is an inherited disorder characterised by mineralisation and fragmentation of elastic fibres in a... (Review)
Review
Pseudoxanthoma elasticum (PXE), also known as Groenblad syndrome, is an inherited disorder characterised by mineralisation and fragmentation of elastic fibres in a number of organs including the skin, eyes and arterial blood vessels. The clinical manifestations of PXE centre on three major organ systems: skin, cardiovascular system and the eyes. This review focuses on the ocular manifestations of pseudoxanthoma elasticum, namely, peau d'orange, angioid streaks and choroidal neovascularisation, the clinical course of patients, the diagnostic approaches and current therapeutic strategies, such as laser photocoagulation whether transpupillary thermotherapy or photodynamic therapy, macular translocation surgery and anti-vascular endothelial growth factor treatment.
Topics: Humans; Pseudoxanthoma Elasticum; Retinal Diseases; Vision Disorders; Visual Acuity
PubMed: 21198842
DOI: 10.1111/j.1444-0938.2010.00559.x -
International Journal of Molecular... Dec 2019Pseudoxanthoma elasticum is a rare disease mainly due to gene mutations and characterized by ectopic biomineralization and fragmentation of elastic fibers resulting in... (Review)
Review
Pseudoxanthoma elasticum is a rare disease mainly due to gene mutations and characterized by ectopic biomineralization and fragmentation of elastic fibers resulting in skin, cardiovascular and retinal calcifications. It has been recently described that pyrophosphate (a calcification inhibitor) deficiency could be the main cause of ectopic calcifications in this disease and in other genetic disorders associated to mutations of or . Patients affected by Pseudoxanthoma Elasticum seem also prone to develop kidney stones originating from papillary calcifications named Randall's plaque, and to a lesser extent may be affected by nephrocalcinosis. In this narrative review, we summarize some recent discoveries relative to the pathophysiology of this mendelian disease responsible for both cardiovascular and renal papillary calcifications, and we discuss the potential implications of pyrophosphate deficiency as a promoter of vascular calcifications in kidney stone formers and in patients affected by chronic kidney disease.
Topics: 5'-Nucleotidase; Diphosphates; GPI-Linked Proteins; Humans; Kidney Calculi; Multidrug Resistance-Associated Proteins; Mutation; Pseudoxanthoma Elasticum; Rare Diseases; Urolithiasis; Vascular Calcification
PubMed: 31861118
DOI: 10.3390/ijms20246353 -
Archives of Disease in Childhood Jul 2005Pseudoxanthoma elasticum (PXE) is a rare multisystem disorder characterised by progressive calcification and fragmentation of elastic fibres. Recent genetic advances... (Review)
Review
Pseudoxanthoma elasticum (PXE) is a rare multisystem disorder characterised by progressive calcification and fragmentation of elastic fibres. Recent genetic advances have identified the underlying defect to the ABCC6 gene on chromosome 16p13.1. Patients typically develop cutaneous, ocular, and cardiovascular manifestations but there is considerable phenotypic variability. The skin changes are usually apparent in adulthood, and rarely observed in childhood. Since the prognosis of PXE largely depends on the extent of extracutaneous organ involvement early recognition, intervention and lifestyle adjustments are important to reduce morbidity. First-degree family members should be carefully examined for any cutaneous or ophthalmologic features of PXE.
Topics: Cardiovascular Diseases; Child; Chromosomes, Human, Pair 16; Eye Diseases; Humans; Multidrug Resistance-Associated Proteins; Pseudoxanthoma Elasticum; Skin Diseases
PubMed: 15970621
DOI: 10.1136/adc.2004.062075 -
Kidney International Jun 2016
Topics: Adult; Blood Gas Analysis; Diagnosis, Differential; Exons; Female; Humans; Kidney; Multidrug Resistance-Associated Proteins; Mutation; Nephrocalcinosis; Parathyroid Hormone; Pseudoxanthoma Elasticum; Retinoscopy; Ultrasonography; Vitamin D
PubMed: 27181788
DOI: 10.1016/j.kint.2015.12.055 -
The Journal of Investigative Dermatology Mar 2016Heritable ectopic mineralization disorders represent a phenotypically diverse group of conditions characterized by deposition of calcium phosphate complexes in soft... (Review)
Review
Heritable ectopic mineralization disorders represent a phenotypically diverse group of conditions characterized by deposition of calcium phosphate complexes in soft connective tissues. The prototype of such conditions is pseudoxanthoma elasticum, and related conditions with overlapping clinical features include generalized arterial calcification of infancy and arterial calcification due to CD73 deficiency. Molecular genetic investigations have revealed mutations in the genes physiologically involved in generation of inorganic pyrophosphate and inorganic phosphate, and the findings suggest a unifying pathomechanism relating to reduced inorganic pyrophosphate/inorganic phosphate ratio. This hypothesis is based on the notion that inorganic pyrophosphate serves as a powerful inhibitor of mineralization, whereas inorganic phosphate is a promineralization factor, and an appropriate inorganic pyrophosphate/inorganic phosphate ratio is critical for prevention of ectopic mineralization under homeostatic conditions.
Topics: 5'-Nucleotidase; Animals; Biomedical Research; Diphosphates; Forecasting; GPI-Linked Proteins; Genetic Predisposition to Disease; Humans; Mice; Mice, Knockout; Molecular Biology; Mutation; Phenotype; Pseudoxanthoma Elasticum; Rare Diseases; Vascular Calcification
PubMed: 26902123
DOI: 10.1016/j.jid.2015.10.065 -
Intractable & Rare Diseases Research Aug 2015Pseudoxantoma elasticum (PXE), also known as Groenblad-Strandberg syndrome, is a rare heritable disease with an estimated prevalence of 1:50,000 in the general... (Review)
Review
Pseudoxantoma elasticum (PXE), also known as Groenblad-Strandberg syndrome, is a rare heritable disease with an estimated prevalence of 1:50,000 in the general population. PXE is considered a prototype of multisystem ectopic mineralization disorders and it is characterized by aberrant mineralization of soft connective tissue with degeneration of the elastic fibers, involving primarily the eyes, the cardiovascular system, and the skin. Cutaneous lesions consist of small, asymptomatic, yellowish papules or larger coalescent plaques, typically located on the neck and the flexural areas. PXE is caused by mutations in the ABCC6 (ATP-binding cassette subfamily C member 6) gene that encodes a transmembrane ATP binding efflux transporter, normally expressed in the liver and the kidney; however, the exact mechanism of ectopic mineralization remains largely unknown. The histological examination of cutaneous lesions, revealing accumulation of pleomorphic elastic structures in middermis, is essential for the definitive diagnosis of PXE, excluding PXE-like conditions. PXE is currently an intractable disease; although the cutaneous findings primarily present a cosmetic problem, they signify the risk for development of ocular and cardiovascular complications associated with considerable morbidity and mortality. The purpose of this review is to present a comprehensive overview of this rare form of hereditary connective tissue disorders, focus on the pathogenesis, the clinical manifestation, and the differential diagnosis of PXE. Emphasis is also placed on the management of cutaneous lesions and treatment perspectives of PXE.
PubMed: 26361562
DOI: 10.5582/irdr.2015.01014 -
Journal of Clinical Pathology Jul 1968Two cases of elastofibroma dorsi are reported and the light and electron microscopic features analysed. The appearances suggest that the characteristic fibres and...
Two cases of elastofibroma dorsi are reported and the light and electron microscopic features analysed. The appearances suggest that the characteristic fibres and globules that stain as for elastin arise by denaturation of collagen. The fibres differ from the elastin of arterial wall, elastotic degeneration of skin, and pseudoxanthoma elasticum. The morphology and clinical behaviour indicate that elastofibroma dorsi is a reactive fibromatosis rather than a true neoplasm.
Topics: Arteries; Back; Collagen; Elastic Tissue; Elastin; Female; Fibroma; Humans; Microscopy, Electron; Middle Aged; Pseudoxanthoma Elasticum; Scapula; Skin
PubMed: 5697345
DOI: 10.1136/jcp.21.4.463 -
Atherosclerosis May 2021Pseudoxanthoma elasticum (PXE) is caused by variants in the ABCC6 gene. It results in calcification in the skin, peripheral arteries and the eyes, but has considerable...
BACKGROUND AND AIMS
Pseudoxanthoma elasticum (PXE) is caused by variants in the ABCC6 gene. It results in calcification in the skin, peripheral arteries and the eyes, but has considerable phenotypic variability. We investigated the association between the ABCC6 genotype and calcification and clinical phenotypes in these different organs.
METHODS
ABCC6 sequencing was performed in 289 PXE patients. Genotypes were grouped as two truncating, mixed, or two non-truncating variants. Arterial calcification mass was quantified on whole body, low dose CT scans; and peripheral arterial disease was measured with the ankle brachial index after treadmill test. The presence of pseudoxanthoma in the skin was systematically scored. Ophthalmological phenotypes were the length of angioid streaks as a measure of Bruchs membrane calcification, the presence of choroidal neovascularizations, severity of macular atrophy and visual acuity. Regression models were built to test the age and sex adjusted genotype-phenotype association.
RESULTS
158 patients (median age 51 years) had two truncating variants, 96 (median age 54 years) a mixed genotype, 18 (median age 47 years) had two non-truncating variants. The mixed genotype was associated with lower peripheral (β: 0.39, 95%CI:-0.62;-0.17) and total (β: 0.28, 95%CI:-0.47;-0.10) arterial calcification mass scores, and lower prevalence of choroidal neovascularizations (OR: 0.41 95%CI:0.20; 0.83) compared to two truncating variants. No association with pseudoxanthomas was found.
CONCLUSIONS
PXE patients with a mixed genotype have less severe arterial and ophthalmological phenotypes than patients with two truncating variants in the ABCC6 gene. Research into environmental and genetic modifiers might provide further insights into the unexplained phenotypic variability.
Topics: Genetic Association Studies; Genotype; Humans; Middle Aged; Peripheral Arterial Disease; Phenotype; Pseudoxanthoma Elasticum
PubMed: 33812167
DOI: 10.1016/j.atherosclerosis.2021.03.012 -
Progress in Retinal and Eye Research May 2024Pseudoxanthoma elasticum (PXE) is an autosomal-recessively inherited multisystem disease. Mutations in the ABCC6-gene are causative, coding for a transmembrane... (Review)
Review
Pseudoxanthoma elasticum (PXE) is an autosomal-recessively inherited multisystem disease. Mutations in the ABCC6-gene are causative, coding for a transmembrane transporter mainly expressed in hepatocytes, which promotes the efflux of adenosine triphosphate (ATP). This results in low levels of plasma inorganic pyrophosphate (PPi), a critical anti-mineralization factor. The clinical phenotype of PXE is characterized by the effects of elastic fiber calcification in the skin, the cardiovascular system, and the eyes. In the eyes, calcification of Bruch's membrane results in clinically visible lesions, including peau d'orange, angioid streaks, and comet tail lesions. Frequently, patients must be treated for secondary macular neovascularization. No effective therapy is available for treating the cause of PXE, but several promising approaches are emerging. Finding appropriate outcome measures remains a significant challenge for clinical trials in this slowly progressive disease. This review article provides an in-depth summary of the current understanding of PXE and its multi-systemic manifestations. The article offers a detailed overview of the ocular manifestations, including their morphological and functional consequences, as well as potential complications. Lastly, previous and future clinical trials of causative treatments for PXE are discussed.
PubMed: 38815804
DOI: 10.1016/j.preteyeres.2024.101274 -
European Journal of Case Reports in... 2020Pseudoxanthoma elasticum (PXE) is a rare genetic disorder characterized by calcification of elastic fibres, skin lesions, fundus lesions and systemic vascular...
UNLABELLED
Pseudoxanthoma elasticum (PXE) is a rare genetic disorder characterized by calcification of elastic fibres, skin lesions, fundus lesions and systemic vascular complications. PXE affects approximately 1 in 160,000 people, typically appearing as a formation of yellow papules containing abnormally calcified elastic fibres. The renal involvement of PXE has been reported. Several factors are known to promote soft tissue and accelerated arterial calcification in chronic kidney disease, including systemic inflammation, altered calcium and phosphate homeostasis, hypertension and a deficiency of endogenous calcification inhibitors. Given the impact of this disease, nephrologists may seek additional supportive features to improve and avoid the risk of complications. Moreover, PXE per se represents an interesting model to evaluate vascular disease in the early stages of renal disease.
LEARNING POINTS
Pseudoxanthoma elasticum represents a rare disease that can involve renal problems.Vascular compromise in patients affected by pseudoxanthoma elasticum shares some components observed in patients with chronic kidney disease.Disorders of mineral and bone metabolism may coexist or be hidden in patients with pseudoxanthoma elasticum.
PubMed: 32015962
DOI: 10.12890/2019_001260