Diagnostic strategy for females suspected of Fabry disease

Balendran, Sukirhini; Oliva, Petra; Sansen, Stefaan; Mechtler, Thomas P.; Streubel, Berthold; Cobos, Paulina Nieves; Lukács, Zoltán; Kasper, David C.

doi:10.1111/cge.13694

Cited by 29 publications

(31 citation statements)

References 21 publications

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“…α‐galactosidase activity below the reference interval for females (1.2‐50.0 µmol/L/h) or Lyso‐GL‐3 above the reference limit (0‐3.5 ng/mL) was considered significant. (the reference interval for female sample α‐galactosidase enzyme activity at ArchiMed changed about the start of June 2019 to 2.8‐50.0 µmol/L/h, so the new reference range was used for any samples after this time) 13 . Next‐generation gene sequencing was performed to validate the results (https://www.archimedlife.com).…”

Section: Methodsmentioning

confidence: 99%

“…Next‐generation gene sequencing was performed to validate the results (https://www.archimedlife.com). 13 Sanger and/or next‐generation sequencing of the entire coding region and flanking intronic regions were performed in all cases. In patients with an unclear outcome after initial genetic sequencing, a further extensive genetic workup was performed for the detection of copy number variations and rare intronic splicing mutations.…”

Section: Methodsmentioning

confidence: 99%

“…(the reference interval for female sample α-galactosidase enzyme activity at ArchiMed changed about the start of June 2019 to 2.8-50.0 µmol/L/h, so the new reference range was used for any samples after this time). 13 Next-generation gene sequencing was performed to validate the results (https://www.archi medli fe.com). 13 Table 1.…”

Section: Female Samplesmentioning

confidence: 99%

“…13 Next-generation gene sequencing was performed to validate the results (https://www.archi medli fe.com). 13 Table 1.…”

Section: Female Samplesmentioning

confidence: 99%

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Identification of patients with Fabry disease using routine pathology results: PATHFINDER (eGFR) study

Reynolds

Tylee²,

Booth³

et al. 2020

Int J Clin Pract

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Aims Lysosomal α‐galactosidase A deficiency (Fabry disease (FD)) was considered an X‐linked recessive disorder but is now viewed as a variable penetrance dominant trait. The prevalence of FD is 1 in 40 000‐117 000 but the ascertainment of late‐onset cases and degree of female penetrance makes this unclear. Its prevalence in the general population, especially in patients with abnormal renal function is unclear. This study attempted to identify the prevalence of FD in patients with abnormal renal function results from laboratory databases. Methods Electronic laboratory databases were interrogated to identify from clinical biochemistry records patients with a phenotype of reduced estimated glomerular filtration rate categorised by age on one occasion or more over a 3‐year time interval. Patients were recalled and a dried blood spot sample was collected for the determination of α‐galactosidase A activity by fluorimetric enzyme assay in men and mass spectrometry assays of α‐galactosidase A and lyso‐globotriaosylceramide (lyso‐GL‐3) concentrations in women. Results Samples were obtained from 1084 patients identified with reduced renal function. No cases of FD were identified in 505 men. From 579 women, one subject with reduced α‐galactosidase activity (1.5 µmol/L/h) and increased Lyso‐GL‐3 (5.5 ng/mL) was identified and shown to be heterozygous for a likely FD pathogenic variant (GLA c.898C>T; p.L300F; Leu300Phe). It was later confirmed that she was a relative of a known affected patient. Conclusions Pathology databases hold routine information that can be used to identify patients with inherited errors of metabolism. Biochemical screening using reduced eGFR alone has a low yield for unidentified cases of Fabry Disease.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Female Samplesmentioning

confidence: 99%

“…13 Next-generation gene sequencing was performed to validate the results (https://www.archi medli fe.com). 13 Table 1.…”

Section: Female Samplesmentioning

confidence: 99%

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Identification of patients with Fabry disease using routine pathology results: PATHFINDER (eGFR) study

Reynolds

Tylee²,

Booth³

et al. 2020

Int J Clin Pract

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“…27,28 A screening strategy in women that improved accuracy in the detection of the disease combined the enzyme activity with lyso-GL3 levels. 29 The confirmatory test is the genetic analysis. This is reserved for women with clinical or laboratory suspicion and for men with low enzyme activity.…”

Section: Definition and General Aspects Of Fdmentioning

confidence: 99%

Renal Manifestations of Fabry Disease: A Narrative Review

Silva

Moura-Neto²,

Reis

et al. 2021

Can J Kidney Health Dis

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Purpose of review: In this narrative review, we describe general aspects, histological alterations, treatment, and implications of Fabry disease (FD) nephropathy. This information should be used to guide physicians and patients in a shared decision-making process. Source of information: Original peer-reviewed articles, review articles, and opinion pieces were identified from PubMed and Google Scholar databases. Only sources in English were accessed. Methods: We performed a focused narrative review assessing the main aspects of FD nephropathy. The literature was critically analyzed from a theoretical and contextual perspective, and thematic analysis was performed. Key findings: FD nephropathy is related to the progressive accumulation of GL3, which occurs in all types of renal cells. It is more prominent in podocytes, which seem to play an important role in the pathogenesis of this nephropathy. A precise detection of renal disorders is of fundamental importance because the specific treatment of FD is usually delayed, making reversibility unlikely and leading to a worse prognosis. Limitations: As no formal tool was applied to assess the quality of the included studies, selection bias may have occurred. Nonetheless, we have attempted to provide a comprehensive review on the topic using current studies from experts in FD and extensive review of the literature.

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Nationwide screening of Fabry disease in patients with hypertrophic cardiomyopathy in Czech Republic

et al. 2022

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Aims Fabry disease (FD) is a rare X‐linked genetic disorder caused by α‐galactosidase A (AGALA) deficiency. Whereas ‘classic’ variant has multisystemic manifestation, the more recently described ‘later‐onset’ variant is characterized by predominant cardiac involvement that often mimics hypertrophic cardiomyopathy (HCM). Methods and results Consecutive unrelated patients with HCM were screened for FD in 16 (out of 17) cardiac centres in the Czech Republic covering specialized cardiology care from June 2017 to December 2018. AGALA activity and globotriaosylsphingosine (lyso‐Gb3) levels were measured in all subjects using the dry blood spot method. FD was suspected in male patients with AGALA activity <1.2 μmol/h/L and in females with either low AGALA activity or lyso‐Gb3 > 3.5 ng/mL. Positive screening results were confirmed by genetic testing. We evaluated 589 patients (390 males, 66%) with HCM (mean maximal myocardial thickness 19.1 ± 4.3 mm). The average age was 58.4 ± 14.7 years. In total, 17 patients (11 males, 6 females) had a positive screening result, and subsequently, six of them (four males and two females) had a genetically confirmed pathogenic GLA mutation (total prevalence of 1.02%). Five of these patients were carrying the p.N215S mutation known to cause a typical later‐onset cardiac FD. Conclusions We confirmed the prevalence of FD repeatedly reported in previous screening programmes (approximately 1% irrespective of gender) in a non‐selected HCM population in Central Europe. Our findings advocate a routine screening for FD in all adult patients with HCM phenotype including both genders. The dry blood spot method used led to identification of clearly pathogenic variants.

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Diagnostic strategy for females suspected of Fabry disease

Cited by 29 publications

References 21 publications

Identification of patients with Fabry disease using routine pathology results: PATHFINDER (eGFR) study

Identification of patients with Fabry disease using routine pathology results: PATHFINDER (eGFR) study

Renal Manifestations of Fabry Disease: A Narrative Review

Nationwide screening of Fabry disease in patients with hypertrophic cardiomyopathy in Czech Republic

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