Screening for Fabry disease in patients undergoing dialysis for chronic renal failure in Turkey: Identification of new case with novel mutation

Okur, İlyas; Ezgu, Fatih Süheyl; Biberoğlu, Gürsel; Tümer, Leyla; Erten, Yasemin; Isitman, Muzeyyen; Eminoğlu, Fatma Tuba; Hasanoğlu, Alev

doi:10.1016/j.gene.2013.05.050

Cited by 36 publications

(30 citation statements)

References 32 publications

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“…Furthermore, in this study the screening of the dialysis population was performed by the dried blood spot method both in male and female patients while it is well established that this method could miss the diagnosis in over onethird of females where mutation analysis is the recommended method of screening [11]. Our study protocol contemplated sequencing of the GLA gene in all patients, thus maximizing the diagnostic yield in some female patients that, even though harboring functionally relevant mutations may exhibit normal enzymatic activity [17].…”

Section: Discussionmentioning

confidence: 99%

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Systematic DNA Study for Fabry Disease in the End Stage Renal Disease Patients from a Southern Italy Area

Zizzo¹,

Testa²,

Colomba³

et al. 2018

Kidney Blood Press Res

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Background/Aims: Fabry disease (FD) is a lysosomal storage disorder characterized by pervasive renal involvement. However, this disease is underdiagnosed in patient with chronic kidney disease (CKD), including those with end stage renal disease (ESRD), so their investigation represents an unexploited opportunity for early diagnosis of the disease and for its identification in relatives of affected patients. Methods: We investigated Fabry disease in a clinical and biological database including ESRD patients of unknown cause in a geographical area with 2 million residents. The study was based on state of art GLA gene sequencing and was extended to relatives of affected ESRD patients. Results: Among ESRD patients qualified for enrollment into this study, a previously undiagnosed young man harboring the mutation p.I91T was identified. The study of the proband's family led to the identification of 8 additional cases. In another ESRD male patient, we identified the functional polymorphism p.D313Y. Furthermore, in 55 ESRD patients (24.2%) we found intronic polymorphisms of uncertain functional relevance in the non-coding regions of the GLA gene. Conclusion: A comprehensive survey of ESRD patients in a geographical area of 2 million residents identified one undiagnosed case of Fabry disease and led to the identification of 8 additional cases among his relatives. Screening protocols starting from the dialysis population and upstream extended to families of affected individuals may be an effective strategy to maximize the early identification of subjects with Fabry disease.

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Section: Discussionmentioning

confidence: 99%

“…Until now only three large scale, comprehensive surveys on the prevalence of Fabry disease in the ESRD population have been made [9][10][11] and these studies identified two to four new, undiagnosed, cases (prevalence ranging from 1.7 per 1000 to 3.4 per 1000 dialysis patients).…”

Section: Introductionmentioning

confidence: 99%

Systematic DNA Study for Fabry Disease in the End Stage Renal Disease Patients from a Southern Italy Area

Zizzo¹,

Testa²,

Colomba³

et al. 2018

Kidney Blood Press Res

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“…Males who are hemizygous for this GLA p.Asn215Ser may present with renal dysfunction at advanced age, with the kidney biopsy showing predominant involvement of podocytes and minimal or absence of GSL deposits in other cell types [62], but only exceptionally [63] has the p.Asn215Ser mutation been identified in FD case-finding studies among HD patients. Indeed, the GLA p.Asn215Ser mutation was not detected in any of 13 large-scale studies screening for FD among patients on RRT that were carried out before 2010 (summarized at [64, 65]), nor in any of those that have been published subsequently [53, 66–70], adding up to more than 20,000 RRT patients screened and more than 30 newly diagnosed carriers of pathogenic GLA mutations. Mutation p.Asn215Ser was also not identified in any of the large stroke patient cohorts of the multinational European “Stroke in Young Fabry Patients study” (n =5023) [52], the “Belgian Fabry study” (n = 1000) [71], the “Stroke Prevention in Young Men Study” (n = 558) [72] and the “PORTYSTROKE study – Screening Genetic Conditions in Portuguese Young Stroke Patients” (n = 493) [45].…”

Section: Discussionmentioning

confidence: 99%

Variations in the GLA gene correlate with globotriaosylceramide and globotriaosylsphingosine analog levels in urine and plasma

Ferreira

Auray‐Blais

Boutin

et al. 2015

Clinica Chimica Acta

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Recent data have shown that lyso-Gb3, the deacylated derivative of globotriaosylceramide (Gb3), is possibly involved in the pathogenesis of Fabry disease (FD) and might be a clinically useful biomarker of its metabolic load. To test this hypothesis, we assayed Gb3 and lyso-Gb3 and related analogs in plasma and/or urine samples of 12 clinically well-characterized subjects carrying several different GLA variant alleles associated with a wide range of residual α-galactosidase A activities. Urinary Gb3 was measured by HPLC–MS/MS; plasma and urinary lyso-Gb3 and related analogs were measured by UPLC–MS/MS. Individual profiles of Gb3 and lyso-Gb3 and related analogs closely correlated with the phenotypic data for each subject, discerning the classical FD patient from the two patients carrying cardiac variants as well as these from all the others without FD. The lyso-Gb3 analog at m/z 836 was found at increased levels only in patients manifesting clinically severe heart disease, irrespective of the pathogenicity of the GLA variant they carried. This finding suggests that this lyso-Gb3 analog might be an earlier biomarker of progressive heart disease, non-specific of the FD cardiomyopathy. The possibility that urinary Gb3 is a specific marker of kidney involvement in FD deserves further study.

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“…Early diagnosis of FD is crucial for commencing early enzyme replacement therapy and improving the natural disease course by preventing progressive organ failure [22]. Although diabetes, hypertension, and chronic glomerulonephritis are the most common causes of ESRD, the causes of primary renal disease in more than 20 % of patients with ESRD are still uncertain [23, 24].…”

Section: Resultsmentioning

confidence: 99%

Identification of a novel GLA mutation (Y88C) in a Korean family with Fabry nephropathy: a case report

et al. 2016

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BackgroundFabry disease is a rare X-linked lysosomal storage disorder caused by α-galactosidase A deficiency. With the advancement of molecular diagnostic tools, more disease-causing mutations in α-galactosidase A (GLA) have been identified in Fabry disease. We found a novel mutation in a Korean family with predominant renal manifestations of the disease.Case presentationA 24-year-old man who wanted to donate a kidney to his 28-year-old brother with end-stage renal disease of unknown cause was evaluated. The 24-year-old man underwent percutaneous renal biopsy because of an accidentally found proteinuria. Electron microscopy of his renal biopsy showed numerous electron-dense multi-lamellar inclusions in the epithelial cytoplasm, typical for Fabry disease. Clinical and laboratory evaluation including the assessment of GLA enzyme activity and direct DNA sequencing in four members of the family were performed. Renal biopsy findings in the two affected male patients were described. Re-evaluation of a renal biopsy specimen of his 28-year-old brother obtained when he was diagnosed with renal failure revealed a very focal area of suspicious multilamellated structures in the Bowman’s space. DNA sequencing on the young man, his brother, and his mother revealed a novel GLA gene mutation, c.263A > G (p.Tyr88Cys). The three all showed decreased α-galactosidase A activity.ConclusionA novel GLA mutation, c.263A > G (p.Tyr88Cys), was found in a Korean family with predominant renal manifestations of Fabry disease.

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Screening for Fabry disease in patients undergoing dialysis for chronic renal failure in Turkey: Identification of new case with novel mutation

Cited by 36 publications

References 32 publications

Systematic DNA Study for Fabry Disease in the End Stage Renal Disease Patients from a Southern Italy Area

Systematic DNA Study for Fabry Disease in the End Stage Renal Disease Patients from a Southern Italy Area

Variations in the GLA gene correlate with globotriaosylceramide and globotriaosylsphingosine analog levels in urine and plasma

Identification of a novel GLA mutation (Y88C) in a Korean family with Fabry nephropathy: a case report

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