PXE

BACKGROUND: Pseudoxanthoma elasticum (PXE) is an autosomal recessive condition caused by mutations in the ABCC6 gene. Ocular features include angioid streaks, peau d'orange fundus, and drusen. We report a novel ABCC6 mutation causing PXE in a patient with a mixed phenotype of PXE and retinitis pigmentosa (RP). CASE: A 37-year-old female presented with decreased peripheral vision and nyctalopia. Ocular imaging revealed angioid streaks emanating from the optic nerve as well as peripheral pigmentary changes and bone spicules...

Ectopic calcification and dysregulated extracellular matrix remodeling are prominent hallmarks of the complex heterogenous pathobiochemistry of pseudoxanthoma elasticum (PXE). The disease arises from mutations in ABCC6 , an ATP-binding cassette transporter expressed predominantly in the liver. Neither its substrate nor the mechanisms by which it contributes to PXE are completely understood. The fibroblasts isolated from PXE patients and Abcc6 -/- mice were subjected to RNA sequencing. A group of matrix metalloproteinases (MMPs) clustering on human chromosome 11q21-23, respectively, murine chromosome 9, was found to be overexpressed...

Pseudoxanthoma elasticum (PXE) is an autosomal recessive genetic disorder characterized by aberrant fragmentation and calcification of elastic fibers, leading to characteristic cutaneous, ophthalmic, and cardiovascular manifestations. PXE demonstrates significant phenotypic variability; involvement of the oral mucosa may be the only clue to the diagnosis. Reports on mucous membrane involvement in PXE are scarce. Here, we present a case of PXE-like changes in the oral cavity. A 70-year-old male patient presented with a painless leukoplakic lesion on the soft palate...

PURPOSE: To describe a patient with concurrent pseudoxanthoma elasticum (PXE) and Cowden syndrome who developed choroidal neovascularization (CNV) secondary to angioid streaks. The CNV presented at a young age and was relatively refractory to intravitreal antivascular endothelial growth factor (anti-VEGF) therapy. METHODS: A retrospective chart review was performed. RESULTS: A 32-year-old man was treated for bilateral sequential CNV over 11 years...

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive disorder caused by mutations in the ATP-binding cassette sub-family C member 6 ( ABCC6 ) gene. Patients with PXE show molecular and clinical characteristics of known premature aging syndromes, such as Hutchinson-Gilford progeria syndrome (HGPS). Nevertheless, PXE has only barely been discussed against the background of premature aging, although a detailed characterization of aging processes in PXE could contribute to a better understanding of its pathogenesis...

PURPOSE: To report an unusual case of pseudoxanthoma elasticum (PXE) presenting with an inflammatory phenotype associated with atypical and rapidly progressive subretinal fibrosis. METHODS: Observational case report. RESULTS: A patient with a history of pseudoxanthoma elasticum presented with rapidly progressive subretinal fibrosis, particularly in the left eye, over the course of one year. The patient was noted at presentation to have intraocular inflammation, outer retinal attenuation, multifocal choroiditis-like lesions, and intraretinal fluid (in the absence of obvious clinical or angiographic signs of exudative CNVM)...

Increased laxity of the skin can be caused by aging, significant weight loss, or defects in the elastic tissue. A 38-year-old female presented with increased laxity of the skin over the neck, thighs, and abdomen for 6 years, associated with headache and blurring of vision for a week. On cutaneous examination, prominent skin folds, laxity, and wrinkles were noted over the neck, abdomen, thighs, and groin, with yellowish papules along the neck creases. Ocular examination revealed features suggestive of angioid streaks...

Pseudoxanthoma elasticum (PXE) is a rare ectopic calcification disorder affecting soft connective tissues that is caused by biallelic ABCC6 mutations. While the underlying pathomechanisms are incompletely understood, reduced circulatory levels of inorganic pyrophosphate (PPi)-a potent mineralization inhibitor-have been reported in PXE patients and were suggested to be useful as a disease biomarker. In this study, we explored the relation between PPi, the ABCC6 genotype and the PXE phenotype. For this, we optimized and validated a PPi measurement protocol with internal calibration that can be used in a clinical setting...

Pseudoxanthoma elasticum (PXE) is characterized by low levels of inorganic pyrophosphate (PPi) and a high activity of tissue-nonspecific alkaline phosphatase (TNAP). Lansoprazole is a partial inhibitor of TNAP. The aim was to investigate whether lansoprazole increases plasma PPi levels in subjects with PXE. We conducted a 2 × 2 randomized, double-blind, placebo-controlled crossover trial in patients with PXE. Patients were allocated 30 mg/day of lansoprazole or a placebo in two sequences of 8 weeks. The primary outcome was the differences in plasma PPi levels between the placebo and lansoprazole phases...

Pseudoxanthoma elasticum (PXE (OMIM 264800)) is an autosomal recessive connective tissue disorder mainly caused by mutations in the ABCC6 gene. PXE results in ectopic calcification primarily in the skin, eye and blood vessels that can lead to blindness, peripheral arterial disease and stroke. Previous studies found correlation between macroscopic skin involvement and severe ophthalmological and cardiovascular complications. This study aimed to investigate correlation between skin calcification and systemic involvement in PXE...

PURPOSE: To quantify choriocapillaris flow alterations in patients with pseudoxanthoma elasticum (PXE) in pre-atrophic stages and its association with structural changes of the choroid and outer retina. METHODS: Thirty-two eyes of 21 patients with PXE and 35 healthy eyes of 35 controls were included. The density of choriocapillaris flow signal deficits (FDs) was quantified on 6 × 6-mm optical coherence tomography angiography (OCTA) images. Spectral-domain optical coherence tomography (SD-OCT) images were analyzed for thicknesses of the choroid and outer retinal microstructure and correlated with choriocapillaris FDs in the respective Early Treatment Diabetic Retinopathy Study subfield...

BACKGROUND: Pseudoxanthoma elasticum (PXE), a monogenic disorder resulting in calcification affecting the skin, eyes and peripheral arteries, is caused by mutations in the ABCC6 gene, and is associated with low plasma inorganic pyrophosphate (PPi ). It is unknown how ABCC6 genotype affects plasma PPi . METHODS: We studied the association of ABCC6 genotype (192 patients with biallelic pathogenic ABCC6 mutations) and PPi levels, and its association with the severity of arterial and ophthalmological phenotypes...

PURPOSE: To report a case of recurrent acute retinopathy associated with pseudoxanthoma elasticum (PXE) and to propose a reappraisal of this entity based on multimodal imaging analysis. METHODS: Retrospective case report. High-resolution optical coherence tomography (High-Res OCT), ultra-widefield imaging, and widefield swept-source OCT-angiography (OCTA) and en face OCT were performed. RESULTS: A man in his 40s diagnosed with PXE and angioid streaks presented with two distinct episodes of acute retinopathy in his right eye during a one-year follow-up period...

PURPOSE: To report the very long-term visual prognosis of choroidal neovascularization (CNV) complicating angioid streaks (AS) in the anti-vascular endothelial growth factor (anti-VEGF) era. METHODS: Retrospective monocentric study aimed at analyzing patients' demographics, CNV features, AS-associated conditions, and previous and current therapies for CNV. The main outcome measures were the quantitative measurement of central retinal pigment epithelial (RPE) atrophy enlargement by comparing the ratio of pixels involved on automated infrared images acquired by spectral-domain optical coherence tomography, and the changes in best-corrected visual acuity (BCVA)...

Pseudoxanthoma elasticum (PXE) is a multisystem, genetic, ectopic mineralization disorder with no effective treatment. Inhibition of tissue-nonspecific alkaline phosphatase (TNAP) may prevent ectopic soft tissue calcification by increasing endogenous pyrophosphate (PPi). This study evaluated the anticalcification effects of DS-1211, an orally administered, potent, and highly selective small molecule TNAP inhibitor, in mouse models of PXE. Calcium content in vibrissae was measured in KK/HlJ and ABCC6-/- mice after DS-1211 administration for 13-14 weeks...

TRAF6 is an adaptor protein involved in signaling pathways that are essential for development and the immune system. It participates in many protein-protein interactions, some of which are mediated by the C-terminal MATH domain, which binds to short peptide segments containing the motif PxExx[FYWHDE], where x is any amino acid. Blocking MATH domain interactions is associated with favorable effects in various disease models. To better define TRAF6 MATH domain binding preferences, we screened a combinatorial library using bacterial cell-surface peptide display...

Pseudoxanthoma elasticum (PXE) is a rare hereditary disorder that causes elastic tissue degeneration in the skin, eyes, and cardiovascular system. Gastrointestinal bleeding and fundus hemorrhage are serious complications associated with PXE prognosis as well as cardiovascular involvement. This is a rare case of acute coronary syndrome in a PXE patient with high bleeding risk. Learning objective: Pseudoxanthoma elasticum (PXE) resulting in acute coronary syndrome (ACS) is rare. Given PXE patients are generally at very high bleeding risk, antithrombotic therapy as secondary prevention after ACS onset should be taken into full consideration...

Pseudoxanthoma elasticum (PXE) is an autosomal recessive multisystem disorder showing phenotypic heterogeneity giving rise to complex comorbidities. The most 'visible' signs are dermatological; however, these may be subtle and hidden from the view of an affected individual. Ophthalmic signs can be easily missed, and here we highlight the importance of a multisystem assessment. We report a patient who developed advanced sight loss due to maculopathy whose underlying PXE aetiology went unnoticed until subtle skin signs were noticed on the lateral aspect of his neck...

Mutations in ABCC6, an ATP-binding cassette transporter with a so far unknown substrate mainly expressed in the liver and kidney, cause pseudoxanthoma elasticum (PXE). Symptoms of PXE in patients originate from the calcification of elastic fibers in the skin, eye, and vessels. Previous studies suggested an involvement of ABCC6 in cholesterol and lipid homeostasis. The intention of this study was to examine the influence of ABCC6 deficiency during adipogenic differentiation of human bone marrow-derived stem cells (hMSCs)...

OBJECTIVES: Pseudoxanthoma elasticum (PXE) is an autosomal recessive metabolic disorder that may be associated with a high prevalence of peripheral artery disease (PAD) and related symptoms. However, the evidence supporting this association is weak, as only small cohort studies are available. Furthermore, limited data are available on outcome of lower limb peripheral arterial interventions (PAI) in patients with PXE. It was our aim to clarify the prevalence of PAD, and the occurrence and outcome of PAI in patients with PXE...