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Romanian Journal of Ophthalmology 2022To present a case of secondary type 2 choroidal neovascularization (CNV) and exudative maculopathy in a patient with Grönblad-Strandberg syndrome. A 37-year-old male...
To present a case of secondary type 2 choroidal neovascularization (CNV) and exudative maculopathy in a patient with Grönblad-Strandberg syndrome. A 37-year-old male was admitted with bilateral progressive painless visual acuity loss and metamorphopsias. A thorough ophthalmologic and clinical examination was performed. Best-corrected visual acuity (BCVA) on presentation was 20/ 200 OD (Oculus Dexter) and 20/ 60 OS (Oculus Sinister). Fundus examination revealed angioid streaks and subretinal hemorrhages on OU (Oculus Uterque), macular fibrosis on OD and "peau d'orange" pigmentary mottling on OS. Leakage areas on fundus fluorescein angiography (FFA) revealed active CNV on OU, which was confirmed by Optical Coherence Tomography (OCT). The presence of typical "plucked chicken" skin lesions in the latero-cervical area and their biopsy confirmed the diagnosis of Pseudoxanthoma elasticum (PXE). Consequently, the diagnosis of Grönblad-Strandberg syndrome was established. Every new diagnosis of angioid streaks entails not only a thorough ophthalmologic evaluation for secondary sight-threatening complications, but also a multidisciplinary evaluation due to the possibility of severe underlying systemic disease. BM = Bruch's membrane, RPE = Retinal Pigmented Epithelium, PXE = Pseudoxanthoma Elasticum, ABCC6 = ATP binding cassette subtype C number 6, CNV = Choroidal Neovascularization, BCVA = Best-Corrected Visual Acuity, OD = Oculus Dexter, OS = Oculus Sinister, OU = Oculus Uterque, FFA = Fundus Fluorescein Angiography, OCT = Optical Coherence Tomography, IPO = Intraocular Pressure, ECG = Electrocardiogram, anti-VEGF = anti-vascular endothelial growth factor.
Topics: Abnormalities, Multiple; Angioid Streaks; Choroidal Neovascularization; Darier Disease; Eyebrows; Fluorescein Angiography; Humans; Male; Pseudoxanthoma Elasticum; Tomography, Optical Coherence
PubMed: 35935090
DOI: 10.22336/rjo.2022.31 -
Dermatology Online Journal Jan 2009A 55-year-old man with progressive loss of vision was referred for dermatology consultation for the evaluation of his skin lesions. The cutaneous examination of the...
A 55-year-old man with progressive loss of vision was referred for dermatology consultation for the evaluation of his skin lesions. The cutaneous examination of the patient revealed multiple small yellow papules, coalescing into plaques, on his neck, axillae and periumbilical regions. He also had redundant skin folds on the axillae. His peripheral pulses and blood pressure were normal. Angioid streaks were found in the ocular fundi. A skin biopsy specimen of the papule showed fragmentation of elastic fibers as well as calcification in the dermis. Given the clinical manifestations and the histopathologic findings, the patient's illness was diagnosed as pseudoxanthoma elasticum. The patient was then sent to undergo a thorough cardiovascular evaluation.
Topics: Humans; Male; Middle Aged; Pseudoxanthoma Elasticum
PubMed: 19281712
DOI: No ID Found -
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 -
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 -
Postgraduate Medical Journal Feb 1970Eight cases of pseudoxanthoma elasticum seen in a Medical Unit in Singapore are described. Of these six belonged to one family. The clinical presentations of these...
Eight cases of pseudoxanthoma elasticum seen in a Medical Unit in Singapore are described. Of these six belonged to one family. The clinical presentations of these cases, especially the first case who was a diagnostic problem for 5 years, are described. Transmission in this family is autosomal-recessive. Eye changes were absent. Skin lesions were minimal and the axillary folds were more involved than the skin of the neck. Of the eight cases, three were asymptomatic except for cutaneous lesions, three had suffered a haemetemesis and four a haemoptysis, while three had mental changes, and two had cerebrovascular involvement. Case 1 had in addition, bleeding from the nose, urinary tract and uterus. She also had a fatty liver, peripheral neuropathy and hysterical fits. Only one case presented as a cosmetic problem. The pathogenesis of PXE is discussed; the primary defect is believed to be in the elastic and not the collagenous tissue.
Topics: Adult; Aged; Female; Genes, Recessive; Hemorrhage; Humans; Male; Mental Disorders; Middle Aged; Pseudoxanthoma Elasticum; Vascular Diseases
PubMed: 5416513
DOI: 10.1136/pgmj.46.532.97 -
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 -
International Journal of Molecular... Dec 2022Ectopic calcification (EC) is characterized by an abnormal deposition of calcium phosphate crystals in soft tissues such as blood vessels, skin, and brain parenchyma. EC... (Review)
Review
Ectopic calcification (EC) is characterized by an abnormal deposition of calcium phosphate crystals in soft tissues such as blood vessels, skin, and brain parenchyma. EC contributes to significant morbidity and mortality and is considered a major health problem for which no effective treatments currently exist. In recent years, growing emphasis has been placed on the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of EC. Impaired mitochondrial respiration and increased levels of reactive oxygen species can be directly linked to key molecular pathways involved in EC such as adenosine triphosphate homeostasis, DNA damage signaling, and apoptosis. While EC is mainly encountered in common diseases such as diabetes mellitus and chronic kidney disease, studies in rare hereditary EC disorders such as pseudoxanthoma elasticum or Hutchinson-Gilford progeria syndrome have been instrumental in identifying the precise etiopathogenetic mechanisms leading to EC. In this narrative review, we describe the current state of the art regarding the role of mitochondrial dysfunction and oxidative stress in hereditary EC diseases. In-depth knowledge of aberrant mitochondrial metabolism and its local and systemic consequences will benefit the research into novel therapies for both rare and common EC disorders.
Topics: Humans; Pseudoxanthoma Elasticum; Progeria; Oxidative Stress; Mitochondria; Reactive Oxygen Species
PubMed: 36499615
DOI: 10.3390/ijms232315288 -
International Journal of Molecular... Apr 2021Pathological (ectopic) mineralization of soft tissues occurs during aging, in several common conditions such as diabetes, hypercholesterolemia, and renal failure and in... (Review)
Review
Pathological (ectopic) mineralization of soft tissues occurs during aging, in several common conditions such as diabetes, hypercholesterolemia, and renal failure and in certain genetic disorders. Pseudoxanthoma elasticum (PXE), a multi-organ disease affecting dermal, ocular, and cardiovascular tissues, is a model for ectopic mineralization disorders. ABCC6 dysfunction is the primary cause of PXE, but also some cases of generalized arterial calcification of infancy (GACI). ABCC6 deficiency in mice underlies an inducible dystrophic cardiac calcification phenotype (DCC). These calcification diseases are part of a spectrum of mineralization disorders that also includes Calcification of Joints and Arteries (CALJA). Since the identification of ABCC6 as the "PXE gene" and the development of several animal models (mice, rat, and zebrafish), there has been significant progress in our understanding of the molecular genetics, the clinical phenotypes, and pathogenesis of these diseases, which share similarities with more common conditions with abnormal calcification. ABCC6 facilitates the cellular efflux of ATP, which is rapidly converted into inorganic pyrophosphate (PPi) and adenosine by the ectonucleotidases NPP1 and CD73 (NT5E). PPi is a potent endogenous inhibitor of calcification, whereas adenosine indirectly contributes to calcification inhibition by suppressing the synthesis of tissue non-specific alkaline phosphatase (TNAP). At present, therapies only exist to alleviate symptoms for both PXE and GACI; however, extensive studies have resulted in several novel approaches to treating PXE and GACI. This review seeks to summarize the role of ABCC6 in ectopic calcification in PXE and other calcification disorders, and discuss therapeutic strategies targeting various proteins in the pathway (ABCC6, NPP1, and TNAP) and direct inhibition of calcification via supplementation by various compounds.
Topics: 5'-Nucleotidase; ATP-Binding Cassette Transporters; Animals; Calcification, Physiologic; Calcinosis; Diphosphates; GPI-Linked Proteins; Humans; Joint Diseases; Mice; Multidrug Resistance-Associated Proteins; Phosphoric Diester Hydrolases; Pseudoxanthoma Elasticum; Pyrophosphatases; Rats; Vascular Calcification; Vascular Diseases
PubMed: 33925341
DOI: 10.3390/ijms22094555 -
Atherosclerosis Jun 2022Pseudoxanthoma elasticum (PXE) is a genetic disorder characterized by systemic calcification of elastin fibers. Additionally, PXE is associated with an increased risk of...
BACKGROUND AND AIMS
Pseudoxanthoma elasticum (PXE) is a genetic disorder characterized by systemic calcification of elastin fibers. Additionally, PXE is associated with an increased risk of stroke. It has been hypothesized that this may be caused by accelerated (intracranial) atherogenesis, as a consequence of specific genetic mutations underlying PXE. Hence, we compared the distribution and burden of intracranial atherosclerosis between PXE patients and healthy controls.
METHODS
Fifty PXE patients and 40 age-and-sex-matched healthy controls (without previous ischemic cerebrovascular disease) underwent 3T MRI to visualize atherosclerotic intracranial vessel wall lesions (VWLs). We compared the presence and burden of VWLs (total and for the anterior cerebral, middle cerebral, intracranial internal carotid, posterior cerebral, and basilar arteries separately) between PXE patients and healthy controls using logistic (presence versus absence) and negative binomial regression models (VWL count) adjusted for relevant confounders. All regressions included group (PXE patients vs. healthy controls) as independent variable.
RESULTS
We found that 34 (68.0%) PXE patients and 28 (70.0%) healthy controls had a VWL (odds ratio for presence 1.06 [95%CI 0.38-2.91]). In addition, the total burden of VWLs was similar between PXE patients (68 VWLs) and healthy controls (73 VWLs, incidence rate ratio for count 0.81 [95%CI 0.55-1.20]). Findings were similar when analyses were stratified for artery.
CONCLUSIONS
The distribution and burden of intracranial atherosclerosis were similar between PXE patients and healthy controls. This implies PXE and its underlying mutations do not involve increased (intracranial) atherogenesis and that vascular calcification or other mechanisms explains the increased stroke risk in PXE.
Topics: Atherosclerosis; Case-Control Studies; Humans; Intracranial Arteriosclerosis; Pseudoxanthoma Elasticum; Stroke; Vascular Calcification
PubMed: 35468517
DOI: 10.1016/j.atherosclerosis.2022.04.014 -
Biology Jan 2024Pseudoxanthoma Elasticum (PXE) is an inherited disease characterized by elastic fiber calcification in the eyes, the skin and the cardiovascular system. PXE results from... (Review)
Review
Pseudoxanthoma Elasticum (PXE) is an inherited disease characterized by elastic fiber calcification in the eyes, the skin and the cardiovascular system. PXE results from mutations in that encodes an ABC transporter primarily expressed in the liver and kidneys. It took nearly 15 years after identifying the gene to better understand the etiology of PXE. ABCC6 function facilitates the efflux of ATP, which is sequentially hydrolyzed by the ectonucleotidases ENPP1 and CD73 into pyrophosphate (PPi) and adenosine, both inhibitors of calcification. PXE, together with General Arterial Calcification of Infancy (GACI caused by mutations) as well as Calcification of Joints and Arteries (CALJA caused by /CD73 mutations), forms a disease continuum with overlapping phenotypes and shares steps of the same molecular pathway. The explanation of these phenotypes place ABCC6 as an upstream regulator of a purinergic pathway (ABCC6 → ENPP1 → CD73 → TNAP) that notably inhibits mineralization by maintaining a physiological Pi/PPi ratio in connective tissues. Based on a review of the literature and our recent experimental data, we suggest that PXE (and GACI/CALJA) be considered as an authentic "purinergic disease". In this article, we recapitulate the pathobiology of PXE and review molecular and physiological data showing that, beyond PPi deficiency and ectopic calcification, PXE is associated with wide and complex alterations of purinergic systems. Finally, we speculate on the future prospects regarding purinergic signaling and other aspects of this disease.
PubMed: 38392293
DOI: 10.3390/biology13020074