scholarly journals Pseudoxanthoma elasticum and skin: Clinical manifestations, histopathology, pathomechanism, perspectives of treatment

2015 ◽  
Vol 4 (3) ◽  
pp. 113-122 ◽  
Author(s):  
Barbara Marconi ◽  
Ivan Bobyr ◽  
Anna Campanati ◽  
Elisa Molinelli ◽  
Veronica Consales ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Pseudoxanthoma Elasticum

scholarly journals Disruption of Abcc6 Transporter in Zebrafish Causes Ocular Calcification and Cardiac Fibrosis

2020 ◽  
Vol 22 (1) ◽  
pp. 278
Author(s):  
Jianjian Sun ◽  
Peilu She ◽  
Xu Liu ◽  
Bangjun Gao ◽  
Daqin Jin ◽  
...  
Keyword(s):  
Vitamin K ◽  
Cardiac Fibrosis ◽  
Clinical Manifestations ◽  
Pseudoxanthoma Elasticum ◽  
Matrix Gla Protein ◽  
Ectopic Calcification ◽  
Transcription Activator ◽  
Multisystem Disorder ◽  
Ectopic Mineralization ◽  
Extensive Calcification

Pseudoxanthoma elasticum (PXE), caused by ABCC6/MRP6 mutation, is a heritable multisystem disorder in humans. The progressive clinical manifestations of PXE are accompanied by ectopic mineralization in various connective tissues. However, the pathomechanisms underlying the PXE multisystem disorder remains obscure, and effective treatment is currently available. In this study, we generated zebrafish abcc6a mutants using the transcription activator-like effector nuclease (TALEN) technique. In young adult zebrafish, abcc6a is expressed in the eyes, heart, intestine, and other tissues. abcc6a mutants exhibit extensive calcification in the ocular sclera and Bruch’s membrane, recapitulating part of the PXE manifestations. Mutations in abcc6a upregulate extracellular matrix (ECM) genes, leading to fibrotic heart with reduced cardiomyocyte number. We found that abcc6a mutation reduced levels of both vitamin K and pyrophosphate (PPi) in the serum and diverse tissues. Vitamin K administration increased the gamma-glutamyl carboxylated form of matrix gla protein (cMGP), alleviating ectopic calcification and fibrosis in vertebrae, eyes, and hearts. Our findings contribute to a comprehensive understanding of PXE pathophysiology from zebrafish models.

Oxidative stress in fibroblasts from patients with pseudoxanthoma elasticum: possible role in the pathogenesis of clinical manifestations

2005 ◽  
Vol 208 (1) ◽  
pp. 54-61 ◽  
Author(s):  
Ivonne Pasquali-Ronchetti ◽  
Maria Inmaculada Garcia-Fernandez ◽  
Federica Boraldi ◽  
Daniela Quaglino ◽  
Dealba Gheduzzi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Manifestations ◽  
Pseudoxanthoma Elasticum

scholarly journals Case Report: Pseudoxanthoma elasticum

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 9
Author(s):  
Catarina Lucas ◽  
João Aranha ◽  
Isabel da Rocha ◽  
Domingos Sousa
Keyword(s):  
Case Report ◽  
Genetic Analysis ◽  
Histological Analysis ◽  
Clinical Manifestations ◽  
Pseudoxanthoma Elasticum ◽  
Cervical Region ◽  
Elastic Fibres ◽  
Incurable Disease ◽  
Initial Stage ◽  
Retinal Complications

Pseudoxanthoma elasticum (PXE) is a rare inherited disorder, characterised by a progressive mineralization and fragmentation of elastic fibres of the skin, retina and cardiovascular system. At an initial stage, the skin usually exhibits distinctive lesions and subsequently extra-dermal manifestations. The diagnosis is based on clinical manifestations, histological analysis of the lesions and genetic analysis. This is a case report of a 12-year-old child complaining of painless, mildly itchy yellow papules in the cervical region with 1 year of evolution. PXE is currently an incurable disease and has a favourable prognosis when cardiovascular and retinal complications are prevented and monitored.

scholarly journals Relationship Between Mitochondrial Structure and Bioenergetics in Pseudoxanthoma elasticum Dermal Fibroblasts

2020 ◽  
Vol 8 ◽  
Author(s):  
Francesco Demetrio Lofaro ◽  
Federica Boraldi ◽  
Maria Garcia-Fernandez ◽  
Lara Estrella ◽  
Pedro Valdivielso ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Clinical Manifestations ◽  
Pseudoxanthoma Elasticum ◽  
Dermal Fibroblasts ◽  
Morphological Data ◽  
Functional Changes ◽  
Ectopic Mineralization ◽  
Mitochondrial Functions ◽  
Extracellular Matrix Components ◽  
Pathologic Calcification

Pseudoxanthoma elasticum (PXE) is a genetic disease considered as a paradigm of ectopic mineralization disorders, being characterized by multisystem clinical manifestations due to progressive calcification of skin, eyes, and the cardiovascular system, resembling an age-related phenotype. Although fibroblasts do not express the pathogenic ABCC6 gene, nevertheless these cells are still under investigation because they regulate connective tissue homeostasis, generating the “arena” where cells and extracellular matrix components can promote pathologic calcification and where activation of pro-osteogenic factors can be associated to pathways involving mitochondrial metabolism. The aim of the present study was to integrate structural and bioenergenetic features to deeply investigate mitochondria from control and from PXE fibroblasts cultured in standard conditions and to explore the role of mitochondria in the development of the PXE fibroblasts’ pathologic phenotype. Proteomic, biochemical, and morphological data provide new evidence that in basal culture conditions (1) the protein profile of PXE mitochondria reveals a number of differentially expressed proteins, suggesting changes in redox balance, oxidative phosphorylation, and calcium homeostasis in addition to modified structure and organization, (2) measure of oxygen consumption indicates that the PXE mitochondria have a low ability to cope with a sudden increased need for ATP via oxidative phosphorylation, (3) mitochondrial membranes are highly polarized in PXE fibroblasts, and this condition contributes to increased reactive oxygen species levels, (4) ultrastructural alterations in PXE mitochondria are associated with functional changes, and (5) PXE fibroblasts exhibit a more abundant, branched, and interconnected mitochondrial network compared to control cells, indicating that fusion prevail over fission events. In summary, the present study demonstrates that mitochondria are modified in PXE fibroblasts. Since mitochondria are key players in the development of the aging process, fibroblasts cultured from aged individuals or aged in vitro are more prone to calcify, and in PXE, calcified tissues remind features of premature aging syndromes; it can be hypothesized that mitochondria represent a common link contributing to the development of ectopic calcification in aging and in diseases. Therefore, ameliorating mitochondrial functions and cell metabolism could open new strategies to positively regulate a number of signaling pathways associated to pathologic calcification.

Pseudoxanthoma Elasticum: Genetics, Clinical Manifestations and Therapeutic Approaches

2009 ◽  
Vol 54 (2) ◽  
pp. 272-285 ◽  
Author(s):  
Robert P. Finger ◽  
Peter Charbel Issa ◽  
Markus S. Ladewig ◽  
Christian Götting ◽  
Christina Szliska ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Pseudoxanthoma Elasticum ◽  
Therapeutic Approaches

scholarly journals Szemfenéki angioid csíkok szisztémás betegségekben

2019 ◽  
Vol 160 (25) ◽  
pp. 994-1000
Author(s):  
Dorottya Kriskó ◽  
Andrea Popper-Sachetti ◽  
Ágnes Sallai ◽  
Gábor Sándor ◽  
Zoltán Zsolt Nagy ◽  
...  
Keyword(s):  
Interdisciplinary Collaboration ◽  
Clinical Manifestations ◽  
Pseudoxanthoma Elasticum ◽  
Posterior Pole ◽  
Morphological Alteration ◽  
Elastic Fibers ◽  
Systemic Diseases ◽  
Angioid Streaks ◽  
Ocular Complication ◽  
Choroidal Rupture

Abstract: Angioid streaks are defined as the special morphological alteration of the fundus; the most common clinical manifestations are irregular, reddish brownish stripes around the optic nerve head or on the posterior pole. On the basis of histological examination, the cause of this phenomenon is the breaks and continuity deficiencies in the thin layer of Bruch membrane caused by the degeneration of elastic fibers. The aim of this study is to present the ocular complication of this rare entity through the description of three cases, and to draw attention to systemic diseases in the background. In our first and third cases, pseudoxanthoma elasticum (Grönblad–Strandberg syndrome) was in the background, while in our second case, hematological disease was confirmed. In our first and second cases, the ocular complication was the choroidal neovascularization, which we treated with intravitreal anti-VEGF injection. In our third case, the choroidal rupture was the ocular complication, caused by trauma. Angioid streaks on the fundus may be sub-phenomena of systemic diseases, the detection, differential diagnosis and treatment require interdisciplinary collaboration between associate physicians. Orv Hetil. 2019; 160(25): 994–1000.

Morphologic alteration in the muscles of patients with hypokalemic periodic paralysis or myopathy

1990 ◽  
Vol 48 (3) ◽  
pp. 222-223
Author(s):  
T. Shimizu ◽  
Y. Muranaka ◽  
I. Ohta ◽  
N. Honda
Keyword(s):  
Clinical Manifestations ◽  
Quadriceps Muscle ◽  
Honeycomb Structure ◽  
Periodic Paralysis ◽  
Ultrastructural Changes ◽  
Hypokalemic Periodic Paralysis ◽  
Electron Microscopic ◽  
Tubular Aggregates ◽  
Hypokalemic Myopathy ◽  
Transmission Electron

There have been many reports on ultrastructural alterations in muscles of hypokalemic periodic paralysis (hpp) and hypokalemic myopathy(hm). It is stressed in those reports that tubular structures such as tubular aggregates are usually to be found in hpp as a characteristic feature, but not in hm. We analyzed the histological differences between hpp and hm, comparing their clinical manifestations and morphologic changes in muscles. Materials analyzed were biopsied muscles from 18 patients which showed muscular symptoms due to hypokalemia. The muscle specimens were obtained by means of biopsy from quadriceps muscle and fixed with 2% glutaraldehyde (pH 7.4) and analyzed by ordinary method and modified Golgimethod. The ultrathin section were examined in JEOL 200CX transmission electron microscopy.Electron microscopic examinations disclosed dilated t-system and terminal cistern of sarcoplasmic reticulum (SR)(Fig 1), and an unique structure like “sixad” was occasionally observed in some specimens (Fig 2). Tubular aggregates (Fig 3) and honeycomb structure (Fig 4) were also common characteristic structures in all cases. These ultrastructural changes were common in both the hypokalemic periodic paralysis and the hypokalemic myopathy, regardless of the time of biopsy or the duration of hypokalemia suffered.

Epigenetic control of TNAP expression in Pseudoxanthoma elasticum fibroblasts

2012 ◽  
Author(s):  
Angela Ostuni ◽  
Vittoria Infantino ◽  
Antonella Salvia ◽  
Rocchina Miglionico ◽  
Federica Boraldi ◽  
...  
Keyword(s):  
Pseudoxanthoma Elasticum ◽  
Epigenetic Control
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