Pseudoxantoma elasticum, as a repetitive upper gastrointestinal hemorrhage cause in a pregnant woman

Göral, Vedat; Demir, Doğan; Tüzün, Yekta; Keklíkçí, Uğur; Büyükbayram, Hüseyin; Bayan, Kadim; Uyar, Aşur

doi:10.3748/wjg.v13.i28.3897

Cited by 13 publications

(5 citation statements)

References 17 publications

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“…Around 15% of PXE patients will experience hemorrhage of the gastrointestinal or urinary tract (especially the stomach), compared with around 0.1% in the general population [ 16 , 25 , 44 ].…”

Section: Clinical Descriptionmentioning

confidence: 99%

Pseudoxanthoma elasticum

Germain

2017

Orphanet J Rare Dis

145

147

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Pseudoxanthoma elasticum (PXE) is a genetic metabolic disease with autosomal recessive inheritance caused by mutations in the ABCC6 gene. The lack of functional ABCC6 protein leads to ectopic mineralization that is most apparent in the elastic tissues of the skin, eyes and blood vessels. The clinical prevalence of PXE has been estimated at between 1 per 100,000 and 1 per 25,000, with slight female predominance. The first clinical sign of PXE is almost always small yellow papules on the nape and sides of the neck and in flexural areas. The papules coalesce, and the skin becomes loose and wrinkled. The mid-dermal elastic fibers are short, fragmented, clumped and calcified. Dystrophic calcification of Bruch’s membrane, revealed by angioid streaks, may trigger choroidal neovascularization and, ultimately, loss of central vision and blindness in late-stage disease. Lesions in small and medium-sized artery walls may result in intermittent claudication and peripheral artery disease. Cardiac complications (myocardial infarction, angina pectoris) are thought to be relatively rare but merit thorough investigation. Ischemic strokes have been reported. PXE is a metabolic disease in which circulating levels of an anti-mineralization factor are low. There is good evidence to suggest that the factor is inorganic pyrophosphate (PPi), and that the circulating low levels of PPi and decreased PPi/Pi ratio result from the lack of ATP release by hepatocytes harboring the mutant ABCC6 protein. However, the substrate(s) bound, transported or modulated by the ABCC6 protein remain unknown. More than 300 sequence variants of the ABCC6 gene have been identified. There is no cure for PXE; the main symptomatic treatments are vascular endothelial growth factor inhibitor therapy (for ophthalmic manifestations), lifestyle, lipid-lowering and dietary measures (for reducing vascular risk factors), and vascular surgery (for severe cardiovascular manifestations). Future treatment options may include gene therapy/editing and pharmacologic chaperone therapy.

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Section: Clinical Descriptionmentioning

confidence: 99%

Pseudoxanthoma elasticum

Germain

2017

Orphanet J Rare Dis

145

147

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“…As a result of these changes, clinical manifestations, including intermittent claudication, loss of peripheral pulses, reno-vascular hypertension, angina pectoris, and rarely, myocardial infarction, can result. There is an increased risk for cerebral ischemic attacks, and mineralized blood vessels of the gastric and intestinal mucosa can rupture leading to gastrointestinal bleeding (Goral et al , 2007). The vascular symptoms can cause significant morbidity and may even result in premature demise of the affected individual.…”

Section: Phenotypic Spectrum Of Pxementioning

confidence: 99%

Pseudoxanthoma Elasticum: Molecular Genetics and Putative Pathomechanisms

Uitto

Jiang

2010

Journal of Investigative Dermatology

134

148

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Pseudoxanthoma elasticum (PXE), a prototypic heritable disorder with ectopic mineralization, manifests with characteristic skin findings, ocular involvement and cardiovascular problems, with considerable morbidity and mortality. The classic forms of PXE are due to loss-of-function mutations in the ABCC6 gene, which encodes ABCC6, a transmembrane efflux transporter expressed primarily in the liver. Several lines of evidence suggest that PXE is a primary metabolic disorder which, in the absence of ABCC6 transporter activity, displays reduced plasma anti-mineralization capacity due to reduced fetuin-A and matrix gla-protein (MGP) levels. MGP requires to be activated by γ-glutamyl carboxylation, a vitamin K-dependent reaction, to serve in anti-mineralization role in the peripheral connective tissue cells. While the molecules transported from the hepatocytes to circulation by ABCC6 in vivo remain unidentified, it has been hypothesized that a critical vitamin K derivative, such as reduced vitamin K conjugated with glutathione, is secreted to circulation physiologically, but not in the absence of ABCC6 transporter activity. As a result, activation of MGP by γ-glutamyl carboxylase is diminished, allowing slow, yet progressive, mineralization of connective tissues characteristic of PXE. Understanding of the pathomechanistic details of PXE provides a basis for development of targeted molecular therapies for this, currently intractable, disease.

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“…[3][4][5][6][7][8][9][10][11][12]23,27 Also, cardiac involvement with left ventricular (LV) diastolic dysfunction has been reported. 28 Importantly, carriers also demonstrate cardiovascular involvement with increased risk of premature CAD, PAD, and anecdotal incidence of ischemic stroke.…”

mentioning

confidence: 99%

Characterization of Cardiovascular Involvement in Pseudoxanthoma Elasticum Families

Campens

Vanakker

Trachet

et al. 2013

ATVB

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Objective-Pseudoxanthoma elasticum (PXE) is an autosomal recessive connective tissue disorder with involvement of the skin, the retina, and the cardiovascular system. Cardiovascular involvement is mainly characterized by mineralization and fragmentation of elastic fibers of blood vessels and premature atherosclerosis. We conducted an ultrasound study to investigate the cardiovascular phenotype and to propose recommendations for the management of patients with PXE and heterozygous ABCC6 mutation carriers. Approach and Results-Thirty-two patients, 23 carriers, and 28 healthy volunteers underwent cardiac and vascular ultrasound studies. Cardiac imaging revealed left ventricular diastolic dysfunction in patients with PXE with a significantly prolonged deceleration time and lower septal early diastolic velocities of the mitral annulus compared with controls. Carriers also demonstrated significantly prolonged deceleration time. Carotid-to-femoral pulse wave velocity was significantly increased in patients with PXE when compared with carriers and controls. Vascular imaging revealed a high prevalence of peripheral artery disease in both patients and carriers and a significantly higher carotid intima-media thickness compared with controls. Conclusions-The results of this study clearly demonstrate impaired left ventricular diastolic function, impairment of the elastic properties of the aorta, and a high prevalence of peripheral artery disease in patients with PXE. Carriers also seem to exhibit a cardiovascular phenotype with mainly mild diastolic dysfunction and accelerated atherosclerosis. Increased awareness for cardiovascular events in both patients and heterozygous carriers is warranted. The ABCC6 gene (chrom. 16p13.1) codes for an ATPdependent transmembrane transporter, which is most abundant in the liver and kidney. Remarkably, the expression of the ABCC6 transporter in tissues clinically affected by PXE is very low. 19 This observation led to the hypothesis that PXE is primarily a metabolic disorder in which circulating serum factor(s) plays a role. 17 Another, and probably complimentary, pathogenetic mechanism is the so-called cellular hypothesis in which fibroblast perturbation may evoke local mineralization and elastic fiber alterations. This hypothesis is based on the observation that elastic fiber alterations are not present homogeneously throughout the skin and blood vessels of patients with PXE, but only in peculiar regions. Moreover, PXE skin fibroblasts exhibit a distinct behavior with altered biosynthetic expression profile and cell-cell and cell-matrix interactions compared with fibroblasts from normal subjects. [20][21][22] This study focuses on the cardiovascular phenotype of patients with PXE and carriers. Cardiovascular changes in patients with PXE are characterized by (1) mineralization and fragmentation of elastic fibers of the internal elastic lamina, medial and adventitial layers of medium-sized arteries and aorta, as well as of the endocardium, pericardium, connective tissue around vessels in t...

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Pseudoxantoma elasticum, as a repetitive upper gastrointestinal hemorrhage cause in a pregnant woman

Cited by 13 publications

References 17 publications

Pseudoxanthoma elasticum

Pseudoxanthoma elasticum

Pseudoxanthoma Elasticum: Molecular Genetics and Putative Pathomechanisms

Characterization of Cardiovascular Involvement in Pseudoxanthoma Elasticum Families

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