ABCC6 mutations and early onset stroke: Two cases of a typical Pseudoxanthoma Elasticum

Bertamino, Marta; Severino, Mariasavina; Grossi, Alice; Rusmini, Marta; Tortora, Domenico; Pederzoli, Silvia; Malattia, Clara; Picco, Paolo; Striano, Pasquale; Ceccherini, Isabella; Rocco, Maja Di; Aiello, Alessia; Banov, Laura; Capra, Valeria; Giacomini, Thea; Lanteri, Paola; Minoia, Francesca; Molinari, Angelo Claudio; Moretti, Paolo; Moscatelli, Andrea; Vari, Maria Stella; Palmieri, Antonella; Pavanello, Marco; Prato, Giulia; Ramenghi, Luca A.; Alessandro, Riccardo; Rossi, Andrea; Uccella, Sarà

doi:10.1016/j.ejpn.2018.04.002

Cited by 15 publications

(9 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PXE patients may therefore suffer from angina pectoris, reduced pulse amplitude, arterial and renovascular hypertension, intermittent claudication, gastro-intestinal hemorrhage, restrictive cardiomyopathy, valvular heart disease, and sudden cardiac death [24,26]. Early-onset arteriosclerosis due to accelerated vascular calcification (VC) may result in early myocardial infarctions and ischemic cerebrovascular disease, of which the risk is almost 4 times greater in PXE patients than in healthy controls [28,31].…”

Section: Mendelian Ectopic Mineralization Diseases and Vitamin Kmentioning

confidence: 99%

The Role of Vitamin K and Its Related Compounds in Mendelian and Acquired Ectopic Mineralization Disorders

Nollet

Gils

Verschuere

et al. 2019

IJMS

View full text Add to dashboard Cite

Ectopic mineralization disorders comprise a broad spectrum of inherited or acquired diseases characterized by aberrant deposition of calcium crystals in multiple organs, such as the skin, eyes, kidneys, and blood vessels. Although the precise mechanisms leading to ectopic calcification are still incompletely known to date, various molecular targets leading to a disturbed balance between pro- and anti-mineralizing pathways have been identified in recent years. Vitamin K and its related compounds, mainly those post-translationally activated by vitamin K-dependent carboxylation, may play an important role in the pathogenesis of ectopic mineralization as has been demonstrated in studies on rare Mendelian diseases, but also on highly prevalent disorders, like vascular calcification. This narrative review compiles and summarizes the current knowledge regarding the role of vitamin K, its metabolism, and associated compounds in the pathophysiology of both monogenic ectopic mineralization disorders, like pseudoxanthoma elasticum or Keutel syndrome, as well as acquired multifactorial diseases, like chronic kidney disease. Clinical and molecular aspects of the various disorders are discussed according to the state-of-the-art, followed by a comprehensive literature review regarding the role of vitamin K in molecular pathophysiology and as a therapeutic target in both human and animal models of ectopic mineralization disorders.

show abstract

Section: Mendelian Ectopic Mineralization Diseases and Vitamin Kmentioning

confidence: 99%

The Role of Vitamin K and Its Related Compounds in Mendelian and Acquired Ectopic Mineralization Disorders

Nollet

Gils

Verschuere

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…The recent development of molecular genetic methods has greatly facilitated the analysis and diagnosis of this group of disorders. For example, the implementation of Next Generation Sequencing (NGS) panels is a costeffective approach to diagnose rare genetic diseases that were once excluded from more common causes of pediatric stroke [31].…”

Section: Genetic Aspects Of Stroke In Pediatric Populationsmentioning

confidence: 99%

The Genetic Basis of Strokes in Pediatric Populations and Insight into New Therapeutic Options

Janković

Petrović²,

Novaković

et al. 2022

IJMS

View full text Add to dashboard Cite

Strokes within pediatric populations are considered to be the 10th leading cause of death in the United States of America, with over half of such events occurring in children younger than one year of life. The multifactorial etiopathology that has an influence on stroke development and occurrence signify the importance of the timely recognition of both modifiable and non-modifiable factors for adequate diagnostic and treatment approaches. The early recognition of a stroke and stroke risk in children has the potential to advance the application of neuroprotective, thrombolytic, and antithrombotic interventions and rehabilitation strategies to the earliest possible timepoints after the onset of a stroke, improving the outcomes and quality of life for affected children and their families. The recent development of molecular genetic methods has greatly facilitated the analysis and diagnosis of single-gene disorders. In this review, the most significant single gene disorders associated with pediatric stroke are presented, along with specific therapeutic options whenever they exist. Besides monogenic disorders that may present with stroke as a first symptom, genetic polymorphisms may contribute to the risk of pediatric and perinatal stroke. The most frequently studied genetic risk factors are several common polymorphisms in genes associated with thrombophilia; these genes code for proteins that are part of the coagulation cascade, fibrolysis, homocystein metabolism, lipid metabolism, or platelets. Single polymorphism frequencies may not be sufficient to completely explain the stroke causality and an analysis of several genotype combinations is a more promising approach. The recent steps forward in our understanding of the disorders underlying strokes has given us a next generation of therapeutics and therapeutic targets by which to improve stroke survival, protect or rebuild neuronal connections in the brain, and enhance neural function. Advances in DNA sequencing and the development of new tools to correct human gene mutations have brought genetic analysis and gene therapy into the focus of investigations for new therapeutic options for stroke patients.

show abstract

“…7 It is associated with numerous complications including characteristic skin lesions (Figure 1A, 1B) and angioid streaks in the retina (Figure 3). Serious vascular complications including myocardial infarction and stroke at a young age have been reported 8 . Because calcified arteries can bleed, hemorrhage from various organs is a reported complication of PXE.…”

Section: In-depth Review Association Between Pseudoxanthoma Elasticum and Bleedingmentioning

confidence: 99%

Association Between Pseudoxanthoma Elasticum and Bleeding

Lebwohl

Phelps

2022

J of Skin

View full text Add to dashboard Cite

Pseudoxanthoma Elasticum (PXE) is a rare genetic disease caused by a mutation of the ABCC6 gene, resulting in calcification of elastic fibers of the skin, eye and other organs and tissues that contain elastin. Because calcified arteries can bleed, hemorrhage from various organs is a reported complication of PXE. We conducted a literature review of all English language published articles reporting bleeding in patients with PXE. In this literature review, we identified 51 papers. Of those, 29 (57%) included at least 1 case of bleeding. Within these 30 papers, bleeding was reported in a total of 130 patients. Of the cases of bleeding, 113 occurred in the gastrointestinal tract, 12 occurred in the brain, 2 in the skin, 1 in the nose, 1 in the gums and 1 in the uterus. Clinicians and patients should be made aware of the risk of these significant complications, to facilitate preventive measures, prompt recognition and treatment.

show abstract

ABCC6 mutations and early onset stroke: Two cases of a typical Pseudoxanthoma Elasticum

Cited by 15 publications

References 5 publications

The Role of Vitamin K and Its Related Compounds in Mendelian and Acquired Ectopic Mineralization Disorders

The Role of Vitamin K and Its Related Compounds in Mendelian and Acquired Ectopic Mineralization Disorders

The Genetic Basis of Strokes in Pediatric Populations and Insight into New Therapeutic Options

Association Between Pseudoxanthoma Elasticum and Bleeding

Contact Info

Product

Resources

About