AIM: To report a case of pseudoxanthoma elasticum (PXE) in a 48 year old woman that presented with bilateral blurry vision. METHODS: A case report RESULTS: A 48-year-old woman presented with bilateral blurry vision an...AIM: To report a case of pseudoxanthoma elasticum (PXE) in a 48 year old woman that presented with bilateral blurry vision. METHODS: A case report RESULTS: A 48-year-old woman presented with bilateral blurry vision and right eye metamorphopsia. The patient had a history of angioid streaks in the left eye ten years ago for which she had received laser surgery and had poor residual vision. Visual acuity was 20/60 in the right eye and count fingers at 6 feet in the left. Fundus examination showed subretinal hemorrhage and macular thickening on the right and a disciform macular scar with focal atrophic pigment epithelial lesions on the left. Both eyes had angioid streaks and peau d’orange pigmentary pattern of the retina. External examination showed several, yellow skin papules and plaques on the lateral and posterior neck, as well as prominent mental creases. Pathologic examination of skin biopsy confirmed the diagnosis of PXE, showing calcium deposition and fragmented, clumped elastic fibers in the deep reticular dermis. She responded well to intravitreal bevacizumab injections and visual acuity improved to 20/25 OD. Preventative care was emphasized and the patient was referred to cardiology, gastroenterology and human genetics for counseling. CONCLUSION: PXE is a multisystem disorder affecting the dermatologic, ocular, and cardiovascular systems. Ophthalmic findings of angioid streaks and choroidal neovascularization in the presence of stereotypical skin changes and prominent mental creases should prompt evaluation for PXE.展开更多
Pseudogenes are frequently encountered noncoding sequences with a high sequence similarity to their protein-coding paralogue.For this reason,their presence is often considered troublesome in molecular diagnostics.In p...Pseudogenes are frequently encountered noncoding sequences with a high sequence similarity to their protein-coding paralogue.For this reason,their presence is often considered troublesome in molecular diagnostics.In pseudoxanthoma elasticum(PXE),a disease predominantly caused by mutations in ATPbinding cassette family C member 6(ABCC6),the presence of two pseudogenes complicates the analysis of sequence data.With whole-exome sequencing(WES)becoming the standard of care in molecular diagnostics,we wanted to evaluate whether this technique is as reliable as gene-specific targeted enrichment analysis for the analysis of ABCC6.We established a PCR-based targeted enrichment and next-generation sequencing testing approach and demonstrated that the ABCC6-specific enrichment combined with the applied mapping algorithm overcomes the complication of ABCC6 pseudogene aspecificities,contrary to WES.We propose a time-and cost-efficient diagnostic strategy for comprehensive and accurate molecular genetic testing of PXE,which is highly automatable.展开更多
Pseudoxanthoma elasticum (PXE) is a hereditary disorder that affects primarily the elastic tissues of skin, eyes and blood vessels. Its estimated prevalence is thought to be 1:25,000 - 100,000. PXE patients also carry...Pseudoxanthoma elasticum (PXE) is a hereditary disorder that affects primarily the elastic tissues of skin, eyes and blood vessels. Its estimated prevalence is thought to be 1:25,000 - 100,000. PXE patients also carry an increased risk for cardiovascular and gastrointestinal diseases. Early diagnosis can play a crucial role in preventing early loss of vision and systemic complications in these patients however despite having characteristic clinical features;it is still to a large extent being under-diagnosed. Here we present two cases of PXE with reduced vision.展开更多
Pseudoxantoma elasticum is a rare, hereditary, multisystemic disease affecting the skin, eye, and cardiovascular system. A twenty-eight-year-old female has presented to emergency unit with the complaint of gastrointes...Pseudoxantoma elasticum is a rare, hereditary, multisystemic disease affecting the skin, eye, and cardiovascular system. A twenty-eight-year-old female has presented to emergency unit with the complaint of gastrointestinal hemorrhage. This patient, who had been monitored in the gastroenterology clinic more than 10 times in the past 8 years, noted a repetitive hemorrhage during her previous pregnancy in her history. The examination of the patient revealed the following signs and symptoms： atrophy in the epithelium of the retina pigment; typical angioid streaks and peau d＇orange finding in the fundus; thinning of the retinal nerve fiber in OCT （optic coherence tomography）; bilateral and reticular papillary lesions with yellowish- color in the neck region （plucked chicken appearance）; presence of bleeding loci in fundus, and nephrocalcinosis in kidneys. In light of these symptoms, the patient was diagnosed with pseudoxantoma elasticum. Skin biopsy confirmed the pseudoxantoma elasticum diagnose. PXE is an uncommon, hereditary disease. Early diagnosis of pseudoxantoma elasticum cases, is important for minimalizing systemic complications and informing the other family members through genetic counseling.展开更多
The present study reports a case of a patient with choroidal neovascularization(CNV)associated with pseudoxanthoma elasticum(PXE).We observed the functional and anatomical improvement of the patient treated with intra...The present study reports a case of a patient with choroidal neovascularization(CNV)associated with pseudoxanthoma elasticum(PXE).We observed the functional and anatomical improvement of the patient treated with intravitreal vascular endothelial growth factor(VEGF)inhibitor bevacizumab.The study also systematically searched the database for similar cases to provide a literature review.Data concerning the clinical features,treatment strategies and outcomes were extracted and analyzed.Retrospective interventional case report and systematic literature review.A 56-year-old healthy Chinese woman with CNV secondary to PXE was reported.Examinations included best corrected visual acuity(BCVA),biomicroscopy,optical coherence tomography(OCT),fluorescein and indocyanine green angiography and digital fundus photography.The patient managed with intravitreal anti-vascular endothelial growth factor(anti-VEGF)injections(bevacizumab 1.25 mg/0.05 m L).The Cochrane Library,Pub Med,OVID,and Up To Date databases were searched using the term pseudoxanthoma elasticum or Gr?nblad-Strandberg syndrome with the limits English.Articles that predated the databases were gathered from current references.Fundus examination revealed angioid streaks bilaterally and CNV in left eye(LE).After the patient underwent three intravitreal injections of bevacizumab,the LE showed absorption of the subretinal fluid and shrinkage of the CNV.Visual acuity(VA)was improved in her treated LE.Bevacizumab treatment was well tolerated with no adverse events reported.Approximately ten articles about 45 patients(49 eyes)describing CNV secondary to angioid streaks in PXE treated with anti-VEGF were found in the literature search.In the present case,bevacizumab of an initial three injection loading dose,achieved maintenance of visual function in the treatment of CNV associated with angioid streaks in PXE.Literature articles concluded that the intravitreal application of anti-VEGF is highly efficient for improving and stabilizing the lesion as well as the eyesight.So we believe that anti-VEGF therapy can be a great choice of treatment for CNV secondary to angioid streaks related PXE.展开更多
Objective:Pseudoxanthoma elasticum(PXE)is a rare genetic disorder caused by loss-of-function mutations in the ABCC6 gene.While PXE is characterized by ectopic mineralization of connective tissues clinically affecting ...Objective:Pseudoxanthoma elasticum(PXE)is a rare genetic disorder caused by loss-of-function mutations in the ABCC6 gene.While PXE is characterized by ectopic mineralization of connective tissues clinically affecting the skin,eyes,and cardiovascular system,kidney stones were reported in some individuals with PXE.The aim of this study is to determine whether kidney stones are an incidental finding or a frequent manifestation of PXE.Methods:We first investigated the genetic basis of two siblings diagnosed with PXE.The younger patient presented with recurrent kidney stones since 8 years old.Secondly,to address whether kidney stones are associated with PXE,the prevalence of kidney stones in a survey cohort of 563 respondents with PXE was compared to that of a general U.S.population survey,National Health and Nutrition Examination Survey,with 28,629 participants.Results:Genetic analysis in both patients identified compound heterozygous mutations in ABCC6,c.2787+1G>T,and c.3774_3775insC.The analysis of participants 20 years old and older revealed that 23.4%of PXE patients had previously had a kidney stone,a significant increase compared to 9.2%in the general population(P<0.01).In addition,17.8%of PXE patients reported their first kidney stone episode before age of 18 years old.Conclusions:PXE correlates with an increased risk of developing kidney stones with considerable morbidity and health-care cost.展开更多
Objective:Pseudoxanthoma elasticum(PXE)is a multisystem heritable disorder caused by mutations in the Abcc6 gene.The disease is characterized by ectopic mineralization of the skin,eyes,and arterial blood vessels.Previ...Objective:Pseudoxanthoma elasticum(PXE)is a multisystem heritable disorder caused by mutations in the Abcc6 gene.The disease is characterized by ectopic mineralization of the skin,eyes,and arterial blood vessels.Previous studies have suggested that cardiovascular complications in patients with PXE are caused in part by premature atherosclerosis.The aim of this study is to determine the effect of an atherogenic diet on ectopic mineralization.Methods:We used Abcc6^(tm1JfK)mice(Abcc6^(-/-)mice)as an established preclinical model of PXE.The offspring at age of 4 weeks were divided into two groups and fed the standard control laboratory diet(control group)and the atherogenic diet.Serum lipid profiles and bile acids were measured,and steatosis and tissue mineralization were evaluated by histopathologic analysis and chemical calcium quantification assay,respectively.Results:After 50-58 weeks of feeding an atherogenic diet,the concentrations of total cholesterol,low-density lipoprotein/very-low-density lipoprotein cholesterol,and bile acids were significantly higher in the Abcc6^(-/-)mice on the atherogenic diet(180.9±14.8 g/L,145.9±12.9 g/L,and 9.7±1.4μmol/L,respectively)than in Abcc6^(-/-)mice on a control diet(85.2±4.8 g/L,25.1±5.5 g/L,and 3.3±0.5μmol/L,respectively)(P<0.001).Hypercholesterolemia was accompanied by extensive lipid accumulation in the liver and aorta,a characteristic feature of steatosis.The direct calcium assay demonstrated significantly increased mineralization of the muzzle skin containing the dermal sheath of vibrissae(57.2±4.4μmol Ca/gram tissue on the atherogenic diet and 43.9±2.2μmol Ca/gram tissue on control diet;P<0.01),a reproducible biomarker of the ectopic mineralization process in these mice.An increased frequency of mineralization was also observed in the kidneys and eyes of mice on the atherogenic diet(P<0.01).Conclusion:These observations suggest that the atherogenic diet caused hypercholesterolemia and accelerated ectopic mineralization in the Abcc6^(-/-)mice.Our findings have clinical implications for patients with PXE,a currently intractable disorder with considerable morbidity and occasional mortality.展开更多
Ectopic mineralization- inappropriate biomineralization in soft tissues- is a frequent finding in physiological aging processes and several common disorders, which can be associated with significant morbidity and mort...Ectopic mineralization- inappropriate biomineralization in soft tissues- is a frequent finding in physiological aging processes and several common disorders, which can be associated with significant morbidity and mortality. Further, pathologic mineralization is seen in several rare genetic disorders, which often present life-threatening phenotypes. These disorders are classified based on the mechanisms through which the mineralization occurs: metastatic or dystrophic calcification or ectopic ossification. Underlying mechanisms have been extensively studied, which resulted in several hypotheses regarding the etiology of mineralization in the extracellular matrix of soft tissue. These hypotheses include intracellular and extracellular mechanisms, such as the formation of matrix vesicles, aberrant osteogenic and chondrogenic signaling, apoptosis and oxidative stress. Though coherence between the different findings is not always clear, current insights have led to improvement of the diagnosis and management of ectopic mineralization patients, thus translating pathogenetic knowledge(variome) to the phenotype(phenome). In this review, we will focus on the clinical presentation, pathogenesis and management of primary genetic soft tissue mineralization disorders. As examples of dystrophic calcification disorders Pseudoxanthoma elasticum, Generalized arterial calcification of infancy, Keutel syndrome, Idiopathic basal ganglia calcification and Arterial calcification due to CD73(NT5E) deficiency will be discussed. Hyperphosphatemic familial tumoral calcinosis will be reviewed as an example of mineralization disorders caused by metastatic calcification.展开更多
Sickle cell disease is an inherited erythrocyte disorder affecting multiple organ systems. As individuals are living well into middle age due to advances in diagnosis and treatment, further disease-related complicatio...Sickle cell disease is an inherited erythrocyte disorder affecting multiple organ systems. As individuals are living well into middle age due to advances in diagnosis and treatment, further disease-related complications are being recognized. This article reviews the cutaneous manifestations of sickle cell disease including leg ulcers and acquired pseudoxanthoma elasticum.展开更多
文摘AIM: To report a case of pseudoxanthoma elasticum (PXE) in a 48 year old woman that presented with bilateral blurry vision. METHODS: A case report RESULTS: A 48-year-old woman presented with bilateral blurry vision and right eye metamorphopsia. The patient had a history of angioid streaks in the left eye ten years ago for which she had received laser surgery and had poor residual vision. Visual acuity was 20/60 in the right eye and count fingers at 6 feet in the left. Fundus examination showed subretinal hemorrhage and macular thickening on the right and a disciform macular scar with focal atrophic pigment epithelial lesions on the left. Both eyes had angioid streaks and peau d’orange pigmentary pattern of the retina. External examination showed several, yellow skin papules and plaques on the lateral and posterior neck, as well as prominent mental creases. Pathologic examination of skin biopsy confirmed the diagnosis of PXE, showing calcium deposition and fragmented, clumped elastic fibers in the deep reticular dermis. She responded well to intravitreal bevacizumab injections and visual acuity improved to 20/25 OD. Preventative care was emphasized and the patient was referred to cardiology, gastroenterology and human genetics for counseling. CONCLUSION: PXE is a multisystem disorder affecting the dermatologic, ocular, and cardiovascular systems. Ophthalmic findings of angioid streaks and choroidal neovascularization in the presence of stereotypical skin changes and prominent mental creases should prompt evaluation for PXE.
基金supported by a Methusalem grant(BOF08/01M01108)from Ghent Universityfunded by Ghent University+1 种基金FWOthe Flemish Government-department EWI。
文摘Pseudogenes are frequently encountered noncoding sequences with a high sequence similarity to their protein-coding paralogue.For this reason,their presence is often considered troublesome in molecular diagnostics.In pseudoxanthoma elasticum(PXE),a disease predominantly caused by mutations in ATPbinding cassette family C member 6(ABCC6),the presence of two pseudogenes complicates the analysis of sequence data.With whole-exome sequencing(WES)becoming the standard of care in molecular diagnostics,we wanted to evaluate whether this technique is as reliable as gene-specific targeted enrichment analysis for the analysis of ABCC6.We established a PCR-based targeted enrichment and next-generation sequencing testing approach and demonstrated that the ABCC6-specific enrichment combined with the applied mapping algorithm overcomes the complication of ABCC6 pseudogene aspecificities,contrary to WES.We propose a time-and cost-efficient diagnostic strategy for comprehensive and accurate molecular genetic testing of PXE,which is highly automatable.
文摘Pseudoxanthoma elasticum (PXE) is a hereditary disorder that affects primarily the elastic tissues of skin, eyes and blood vessels. Its estimated prevalence is thought to be 1:25,000 - 100,000. PXE patients also carry an increased risk for cardiovascular and gastrointestinal diseases. Early diagnosis can play a crucial role in preventing early loss of vision and systemic complications in these patients however despite having characteristic clinical features;it is still to a large extent being under-diagnosed. Here we present two cases of PXE with reduced vision.
文摘Pseudoxantoma elasticum is a rare, hereditary, multisystemic disease affecting the skin, eye, and cardiovascular system. A twenty-eight-year-old female has presented to emergency unit with the complaint of gastrointestinal hemorrhage. This patient, who had been monitored in the gastroenterology clinic more than 10 times in the past 8 years, noted a repetitive hemorrhage during her previous pregnancy in her history. The examination of the patient revealed the following signs and symptoms： atrophy in the epithelium of the retina pigment; typical angioid streaks and peau d＇orange finding in the fundus; thinning of the retinal nerve fiber in OCT （optic coherence tomography）; bilateral and reticular papillary lesions with yellowish- color in the neck region （plucked chicken appearance）; presence of bleeding loci in fundus, and nephrocalcinosis in kidneys. In light of these symptoms, the patient was diagnosed with pseudoxantoma elasticum. Skin biopsy confirmed the pseudoxantoma elasticum diagnose. PXE is an uncommon, hereditary disease. Early diagnosis of pseudoxantoma elasticum cases, is important for minimalizing systemic complications and informing the other family members through genetic counseling.
文摘The present study reports a case of a patient with choroidal neovascularization(CNV)associated with pseudoxanthoma elasticum(PXE).We observed the functional and anatomical improvement of the patient treated with intravitreal vascular endothelial growth factor(VEGF)inhibitor bevacizumab.The study also systematically searched the database for similar cases to provide a literature review.Data concerning the clinical features,treatment strategies and outcomes were extracted and analyzed.Retrospective interventional case report and systematic literature review.A 56-year-old healthy Chinese woman with CNV secondary to PXE was reported.Examinations included best corrected visual acuity(BCVA),biomicroscopy,optical coherence tomography(OCT),fluorescein and indocyanine green angiography and digital fundus photography.The patient managed with intravitreal anti-vascular endothelial growth factor(anti-VEGF)injections(bevacizumab 1.25 mg/0.05 m L).The Cochrane Library,Pub Med,OVID,and Up To Date databases were searched using the term pseudoxanthoma elasticum or Gr?nblad-Strandberg syndrome with the limits English.Articles that predated the databases were gathered from current references.Fundus examination revealed angioid streaks bilaterally and CNV in left eye(LE).After the patient underwent three intravitreal injections of bevacizumab,the LE showed absorption of the subretinal fluid and shrinkage of the CNV.Visual acuity(VA)was improved in her treated LE.Bevacizumab treatment was well tolerated with no adverse events reported.Approximately ten articles about 45 patients(49 eyes)describing CNV secondary to angioid streaks in PXE treated with anti-VEGF were found in the literature search.In the present case,bevacizumab of an initial three injection loading dose,achieved maintenance of visual function in the treatment of CNV associated with angioid streaks in PXE.Literature articles concluded that the intravitreal application of anti-VEGF is highly efficient for improving and stabilizing the lesion as well as the eyesight.So we believe that anti-VEGF therapy can be a great choice of treatment for CNV secondary to angioid streaks related PXE.
基金This study was supported by the PXE International,NIH/NIAMS grants R01AR028450(JU)and R01AR072695(JU and QL)The authors thank our patients for their participation in our studies.Carol Kelly assisted in manuscript preparation.
文摘Objective:Pseudoxanthoma elasticum(PXE)is a rare genetic disorder caused by loss-of-function mutations in the ABCC6 gene.While PXE is characterized by ectopic mineralization of connective tissues clinically affecting the skin,eyes,and cardiovascular system,kidney stones were reported in some individuals with PXE.The aim of this study is to determine whether kidney stones are an incidental finding or a frequent manifestation of PXE.Methods:We first investigated the genetic basis of two siblings diagnosed with PXE.The younger patient presented with recurrent kidney stones since 8 years old.Secondly,to address whether kidney stones are associated with PXE,the prevalence of kidney stones in a survey cohort of 563 respondents with PXE was compared to that of a general U.S.population survey,National Health and Nutrition Examination Survey,with 28,629 participants.Results:Genetic analysis in both patients identified compound heterozygous mutations in ABCC6,c.2787+1G>T,and c.3774_3775insC.The analysis of participants 20 years old and older revealed that 23.4%of PXE patients had previously had a kidney stone,a significant increase compared to 9.2%in the general population(P<0.01).In addition,17.8%of PXE patients reported their first kidney stone episode before age of 18 years old.Conclusions:PXE correlates with an increased risk of developing kidney stones with considerable morbidity and health-care cost.
基金This study was supported by National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases grants(No.R01AR055225 to JU,K01AR064766 to QL,and R01AR072695 to JU and QL).
文摘Objective:Pseudoxanthoma elasticum(PXE)is a multisystem heritable disorder caused by mutations in the Abcc6 gene.The disease is characterized by ectopic mineralization of the skin,eyes,and arterial blood vessels.Previous studies have suggested that cardiovascular complications in patients with PXE are caused in part by premature atherosclerosis.The aim of this study is to determine the effect of an atherogenic diet on ectopic mineralization.Methods:We used Abcc6^(tm1JfK)mice(Abcc6^(-/-)mice)as an established preclinical model of PXE.The offspring at age of 4 weeks were divided into two groups and fed the standard control laboratory diet(control group)and the atherogenic diet.Serum lipid profiles and bile acids were measured,and steatosis and tissue mineralization were evaluated by histopathologic analysis and chemical calcium quantification assay,respectively.Results:After 50-58 weeks of feeding an atherogenic diet,the concentrations of total cholesterol,low-density lipoprotein/very-low-density lipoprotein cholesterol,and bile acids were significantly higher in the Abcc6^(-/-)mice on the atherogenic diet(180.9±14.8 g/L,145.9±12.9 g/L,and 9.7±1.4μmol/L,respectively)than in Abcc6^(-/-)mice on a control diet(85.2±4.8 g/L,25.1±5.5 g/L,and 3.3±0.5μmol/L,respectively)(P<0.001).Hypercholesterolemia was accompanied by extensive lipid accumulation in the liver and aorta,a characteristic feature of steatosis.The direct calcium assay demonstrated significantly increased mineralization of the muzzle skin containing the dermal sheath of vibrissae(57.2±4.4μmol Ca/gram tissue on the atherogenic diet and 43.9±2.2μmol Ca/gram tissue on control diet;P<0.01),a reproducible biomarker of the ectopic mineralization process in these mice.An increased frequency of mineralization was also observed in the kidneys and eyes of mice on the atherogenic diet(P<0.01).Conclusion:These observations suggest that the atherogenic diet caused hypercholesterolemia and accelerated ectopic mineralization in the Abcc6^(-/-)mice.Our findings have clinical implications for patients with PXE,a currently intractable disorder with considerable morbidity and occasional mortality.
基金Supported by The Research Foundation Flanders(FWO)(FWO14/ASP/084),Vanakker OM is a senior clinical investigator at the Fund for Scientific Research-FlandersContract grant sponsor:FWO grant No G.0241.11NMethusalem grant No.08/01M01108
文摘Ectopic mineralization- inappropriate biomineralization in soft tissues- is a frequent finding in physiological aging processes and several common disorders, which can be associated with significant morbidity and mortality. Further, pathologic mineralization is seen in several rare genetic disorders, which often present life-threatening phenotypes. These disorders are classified based on the mechanisms through which the mineralization occurs: metastatic or dystrophic calcification or ectopic ossification. Underlying mechanisms have been extensively studied, which resulted in several hypotheses regarding the etiology of mineralization in the extracellular matrix of soft tissue. These hypotheses include intracellular and extracellular mechanisms, such as the formation of matrix vesicles, aberrant osteogenic and chondrogenic signaling, apoptosis and oxidative stress. Though coherence between the different findings is not always clear, current insights have led to improvement of the diagnosis and management of ectopic mineralization patients, thus translating pathogenetic knowledge(variome) to the phenotype(phenome). In this review, we will focus on the clinical presentation, pathogenesis and management of primary genetic soft tissue mineralization disorders. As examples of dystrophic calcification disorders Pseudoxanthoma elasticum, Generalized arterial calcification of infancy, Keutel syndrome, Idiopathic basal ganglia calcification and Arterial calcification due to CD73(NT5E) deficiency will be discussed. Hyperphosphatemic familial tumoral calcinosis will be reviewed as an example of mineralization disorders caused by metastatic calcification.
文摘Sickle cell disease is an inherited erythrocyte disorder affecting multiple organ systems. As individuals are living well into middle age due to advances in diagnosis and treatment, further disease-related complications are being recognized. This article reviews the cutaneous manifestations of sickle cell disease including leg ulcers and acquired pseudoxanthoma elasticum.
