Characterization of Classical and Nonclassical Fabry Disease: A Multicenter Study

Arends, Maarten; Wanner, Christoph; Hughes, D.A.; Mehta, Atul; Oder, Daniel; Watkinson, Oliver; Elliott, Perry; Linthorst, Gabor E.; Wijburg, Frits A.; Biegstraaten, Marieke; Hollak, Carla E. M.

doi:10.1681/asn.2016090964

Cited by 268 publications

(261 citation statements)

References 48 publications

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“…However, more comprehensive and critical investigations showed that these variants do not definitively lead to Fabry disease-related complications. 31,36 D83N is a novel variant, but the patient had normal urine Gb 3 levels and no other characteristics of Fabry disease. This variant was found to have high residual α-galactosidase A activity in the HEK-293 in vitro assay.…”

Section: Discussionmentioning

confidence: 89%

Low frequency of Fabry disease in patients with common heart disease

Schiffmann

Swift

McNeill

et al. 2018

Genetics in Medicine

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Purpose: To test the hypothesis that undiagnosed patients with Fabry disease exist among patients affected by common heart disease.Methods: Globotriaosylceramide in random whole urine using tandem mass spectroscopy, α-galactosidase A activity in dried blood spots, and next-generation sequencing of pooled or individual genomic DNA samples supplemented by Sanger sequencing.Results: We tested 2,256 consecutive patients: 852 women (median age 65 years (19-95)) and 1,404 men (median age 65 years (21-92)). The primary diagnoses were coronary artery disease (n = 994), arrhythmia (n = 607), cardiomyopathy (n = 138), and valvular disease (n = 568). Urinary globotriaosylceramide was elevated in 15% of patients and 15 males had low α-galactosidase A activity. GLA variants found included R118C (n = 2), D83N, and D313Y (n = 7);

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Section: Discussionmentioning

confidence: 89%

Low frequency of Fabry disease in patients with common heart disease

Schiffmann

Swift

McNeill

et al. 2018

Genetics in Medicine

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“…All the patients with diagnosis of classical FD [18][19][20] attending the Fabry Center of the Federico II University of Naples between 2001 and 2016 were considered for recruitment. We excluded patients with late-onset or non-classical [21,22] variants of FD (n = 23), patients with additional renal involvement (unilateral nephrectomy and congenital anomaly; n = 7) and diabetes (n = 2).…”

Section: Patient Population and Methodsmentioning

confidence: 99%

Glomerular Hyperfiltration: An Early Marker of Nephropathy in Fabry Disease

Riccio

Sabbatini²,

Bruzzese³

et al. 2018

Nephron

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Background and objectives: Progressive nephropathy is one of the main features of Fabry disease (FD). It has been supposed that an early phase, clinically silent disease occurs in childhood and adolescence and is characterized by glomerular hyperfiltration (HF). Surprisingly, although HF has been reported in several studies, its prevalence is at present unknown. The focus of our study was to determine the prevalence of HF in a cohort of patients with FD and to identify the factors associated with a high risk of HF. Methods: To address this issue, a retrospective observational study of 87 patients with genetically confirmed FD was performed. HF was defined as an estimated glomerular filtration rate (eGFR) > 130 mL/min/1.73 m² corrected for age (> 40 years: –1 mL/min/1.73 m²/year). Results: HF occurred in 21 patients (24% of our population), and increased to 50% when only young adults were considered. Hyperfiltrating patients were younger and had lower proteinuria levels than those without HF. The prevalence of cardiovascular and other manifestations of FD was significantly lower in hyperfiltering patients. Conclusions: Our study showed a negative correlation between eGFR and age, and with proteinuria levels and the presence of cardiovascular and other manifestations of FD. These data favor the view that HF in Fabry patients could be related predominantly to a predisease state. Even in the absence of a “measured” GFR, HF should be regarded as an early marker of Fabry nephropathy, and its recognition and confirmation by true GFR seems a relevant feature to address the issue of the potential benefit of nephroprotective treatments at the early stage of Fabry nephropathy.

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“…Reduced or absent activity of this enzyme results in the accumulation of glycosphingolipids such as globotriaosylceramide (Gb3) in various cells types throughout the body. This leads to cardiac, renal, and cerebral involvement and complications …”

Section: Introductionmentioning

confidence: 99%

The Mini Mental State Examination does not accurately screen for objective cognitive impairment in Fabry Disease

et al. 2019

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Fabry disease (FD) patients may suffer from objective cognitive impairment (OCI). This study assessed the accuracy of the Mini Mental State Examination (MMSE) to screen for OCI in FD patients. Presence or absence of OCI was established using a neuropsychological test battery. For different MMSE cutoffs sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and clinical utility index (CUI) to identify OCI were calculated. Eighty‐one patients were included (mean age 44.5 ± 14.3, 35% men, 74% classical phenotype) of which 13 patients (16%) had OCI. The median MMSE score was 29 (range: 25‐30). MMSE cutoffs ≤28 and ≤29 had the highest sensitivity and specificity, with higher specificity reached at cutoff ≤28 (sensitivity: .46, specificity: .73) and higher sensitivity at cutoff ≤29 (sensitivity: .92, specificity: .40). PPV was low for both cutoffs (PPV ≤28: .25, PPV ≤29: .23) resulting in a low positive CUI (case finding ability). The results of our study indicate that the MMSE does not accurately screen for OCI in FD, with poor sensitivity‐specificity trade‐off at all cutoffs. The low PPV shows that the majority of FD patients that score below the cutoffs do not suffer from OCI. Administering the MMSE as a screening test will lead to unnecessary referrals for neuropsychological testing, which is time consuming and burdensome. Screening tools designed to accurately detect mild (executive) impairment might prove more appropriate to screen for OCI in FD.

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Characterization of Classical and Nonclassical Fabry Disease: A Multicenter Study

Cited by 268 publications

References 48 publications

Low frequency of Fabry disease in patients with common heart disease

Low frequency of Fabry disease in patients with common heart disease

Glomerular Hyperfiltration: An Early Marker of Nephropathy in Fabry Disease

The Mini Mental State Examination does not accurately screen for objective cognitive impairment in Fabry Disease

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