Chronic kidney disease and an uncertain diagnosis of Fabry disease: Approach to a correct diagnosis

Tol, Linda van der; Svarstad, Einar; Ortíz, Alberto; Tøndel, Camilla; Oliveira, João Paulo; Vogt, Liffert; Waldek, Stephen; Hughes, D.A.; Lachmann, Robin; Terryn, Wim; Hollak, Carla E. M.; Florquin, Sandrine; Weerman, Marius A. van den Bergh; Wanner, Christoph; West, Michael; Biegstraaten, Marieke; Linthorst, Gabor E.

doi:10.1016/j.ymgme.2014.08.007

Cited by 55 publications

(39 citation statements)

References 32 publications

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“…A clinical stereomicroscopy score of 0/3 was determined, which mirrored the subsequent histologic podocyte inclusion score of 0 (semi-thin toluidine blue section). Because of this finding, in combination with an absence of all rel-evant Fabry-related clinical findings [3], the diagnosis Fabry disease was rejected (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

“…The presence of characteristic Gb3 deposits on electron microscopy has been defined as the gold standard for diagnosis of Fabry nephropathy [2,3]. The importance of kidney biopsies in diagnosis of Fabry disease as well as its potential in the assessment of therapeutic effect of enzyme replacement therapy has recently been highlighted [3,4]. Multifactorial mechanisms are involved in progressive Fabry nephropathy affecting glo-merular, vascular and interstitial compartments, many of which are only partly understood [5].…”

Section: Introductionmentioning

confidence: 99%

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Bedside Stereomicroscopy of Fabry Kidney Biopsies: An Easily Available Method for Diagnosis and Assessment of Sphingolipid Deposits

Svarstad¹,

Leh²,

Skrunes³

et al. 2017

Nephron

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Background/Aims: A previous case report found stereomicroscopic changes typical for Fabry disease in a kidney biopsy. This case series evaluates an expanded diagnostic capacity of the method. Methods: Bedside stereomicroscopy was performed in a cross-sectional prospective study of 31 consecutive enzyme-treated or treatment-naïve male (n = 14) and female Fabry disease patients. The burden of glomerular storage material was scored semiquantitatively on a visual analog scale (range 0-3) and a blinded comparison was done with a reference histologic method. Results: Significant correlations (p < 0.001) were found between the stereomicroscopic scoring of glomerular characteristic white storage material and the amount of podocyte globotriaosylceramide (Gb3) deposits scored by standardized light microscopy. The bedside method correctly identified the variability of podocyte Gb3 accumulation after 10 years of identical agalsidase therapy in 2 brothers aged 24 and 27 years, and also identified tubular cell deposits. Stereomicroscopy correctly verified the absence of sphingolipid deposits in the biopsy of a female index patient with a genetic variant of unknown significance, and the diagnosis of Fabry disease was finally discarded. Conclusions: Bedside stereomicroscopy of kidney biopsies is an easily available, low-cost microscopy method handled by the clinician. The method carries a high diagnostic sensitivity for Fabry disease, reducing the risk of misdiagnosis in previously unknown cases. An expanded yield of the method is suggested, including the grading of the podocyte Gb3 burden and assessment of effectiveness of enzyme replacement therapy. We recommend the method as complementary to current standard histologic evaluation of Fabry kidney biopsies.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bedside Stereomicroscopy of Fabry Kidney Biopsies: An Easily Available Method for Diagnosis and Assessment of Sphingolipid Deposits

Svarstad¹,

Leh²,

Skrunes³

et al. 2017

Nephron

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“…For this purpose, detection of high levels of GL-3 or Lyso-GL3 in plasma, or urine, has been proposed among the criteria to support the diagnosis of FD [14]. We agree that evaluation of Lyso-GL3 levels would have been important for investigating the pathogenicity of the novel mutation, C52F; unfortunately, it was not possible to perform this analysis in the index case because he died soon after the diagnosis and there was no serum available from him to perform a postmortem analysis.…”

Section: Resultsmentioning

confidence: 99%

Targeted Screening of Fabry Disease in Male Hemodialysis Patients in Brazil Highlights Importance of Family Screening

Silva

Barreto

Reis

et al. 2016

Nephron

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Introduction: Fabry disease (FD) is a lysosomal storage disorder caused by enzyme α galactosidase A (α-Gal A) deficiency due to mutations in the galactosidase alpha (GLA) gene. It leads to damage several organs, such as the kidneys, due to progressive accumulation of glycosphingolipids. Objective: To estimate the prevalence of FD among male hemodialysis (HD) patients in a northern state of Brazil. Methods: Screening was performed using a dried blood spot on filter paper to identify patients with low α-Gal A enzyme activity (≤2.2 µmol/l/h). Those with low enzyme activity underwent genetic analysis of the GLA gene. Family screening was conducted in the index cases. Results: 2,583 male HD patients (age: 52 (18-91 years)) were screened. The α-Gal A assay identified 72 males (2.78%) with low enzyme activity. Genotyping identified 3 patients with GLA mutations: W204X, A368T, both previously reported; and C52F, a novel missense mutation. Only the patient with W204X mutation had classic FD. The prevalence rate was 0.12%. Family screening of the index cases identified 23 family members with the same mutations. Conclusions: The prevalence of FD amongst male HD patients found in the Northern of Brazil was low (0.12%). However, family screening of the 3 index cases identified family members at an early stage of the disease, which may benefit from earlier treatment.

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“…4) Renal biopsy. A panel of nephrologists and international experts on FD indicated that a biopsy of the kidney with electron microscopy assessment is currently the only available tool that can reliably confirm or exclude FD nephropathy and should be considered in all patients without a classical pattern of disease manifestations, a GLA variant and CKD who have an uncertain diagnosis of FD [58]. This technique is also feasible for the routine study of paraffin-embedded kidney biopsies that have been immunostained with an anti-Gb3 antibody [59].…”

Section: Biomarkers and Diagnostic Studies For Fabry Nephropathymentioning

confidence: 99%

Fabry Nephropathy: An Evidence-Based Narrative Review

Pino

Andrés

Bernabeu

et al. 2018

Kidney Blood Press Res

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Chronic kidney disease and an uncertain diagnosis of Fabry disease: Approach to a correct diagnosis

Cited by 55 publications

References 32 publications

Bedside Stereomicroscopy of Fabry Kidney Biopsies: An Easily Available Method for Diagnosis and Assessment of Sphingolipid Deposits

Bedside Stereomicroscopy of Fabry Kidney Biopsies: An Easily Available Method for Diagnosis and Assessment of Sphingolipid Deposits

Targeted Screening of Fabry Disease in Male Hemodialysis Patients in Brazil Highlights Importance of Family Screening

Fabry Nephropathy: An Evidence-Based Narrative Review

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