Prevalence of Fabry Disease and Outcomes in Young Canadian Patients With Cryptogenic Ischemic Cerebrovascular Events

Lanthier, Sylvain; Saposnik, Gustavo; Lebovic, Gerald; Pope, Karen L.; Selchen, Daniel; Moore, David F.

doi:10.1161/strokeaha.116.016083

Cited by 24 publications

(31 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The actual frequency of patients identified was lower than the reported frequency. 31 Similarly, the identification frequencies in the recent report 32 and the present study were low.…”

Section: Discussionsupporting

confidence: 46%

Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis

Maruyama

Miyata

Mikame

et al. 2019

Genetics in Medicine

View full text Add to dashboard Cite

PurposePlasma globotriaosylsphingosine (lyso-Gb3) is a promising secondary screening biomarker for Fabry disease. Here, we examined its applicability as a primary screening biomarker for classic and late-onset Fabry disease in males and females.MethodsBetween 1 July 2014 and 31 December 2015, we screened 2,360 patients (1,324 males) referred from 169 Japanese specialty clinics (cardiology, nephrology, neurology, and pediatrics), based on clinical symptoms suggestive of Fabry disease. We used the plasma lyso-Gb3 concentration, α-galactosidase A (α-Gal A) activity, and analysis of the α-Gal A gene (GLA) for primary and secondary screens, respectively.ResultsOf 8 males with elevated lyso-Gb3 levels (≥2.0 ng ml) and low α-Gal A activity (≤4.0 nmol h ml), 7 presented a GLA mutation (2 classic and 5 late-onset). Of 15 females with elevated lyso-Gb3, 7 displayed low α-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 8 exhibited normal α-Gal A activity (1 with a classic GLA mutation and 3 with genetic variants of uncertain significance).ConclusionPlasma lyso-Gb3 is a potential primary screening biomarker for classic and late-onset Fabry disease probands.Genet Med advance online publication, 15 March 2018; doi:10.1038/gim.2018.31.

show abstract

“…The actual frequency of patients identified was lower than the reported frequency. 31 Similarly, the identification frequencies in the recent report 32 and the present study were low.…”

Section: Discussionsupporting

confidence: 46%

Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis

Maruyama

Miyata

Mikame

et al. 2019

Genetics in Medicine

View full text Add to dashboard Cite

show abstract

“…The result of the present study is in keeping with other population-based studies where a similar issue was investigated. In a Canadian cohort of cryptogenic ischemic vascular events, the prevalence of Fabry disease was low, estimated to be around 0.3% [3,4]. Almost similar findings were reported in other studies among different populations [5,6,7].…”

Section: Discussionsupporting

confidence: 83%

The Prevalence of Fabry Disease Among Young Cryptogenic Stroke Patients

Alhazzaa

Mujtaba

Aljohani

et al. 2020

Cureus

View full text Add to dashboard Cite

Introduction Fabry disease is a metabolic storage disorder that causes disorders in multiple organs including the brain. Data regarding the prevalence of the disease among the Saudi stroke population is scarce. Hence, tests for the same are not conducted on a regular basis when investigating stroke of uncertain cause. Our study aimed to provide insight into whether testing for Fabry disease is justifiable in cryptogenic stroke patients who have no other features of the disease. Method This was a prospective study conducted at a single stroke center. We included young patients between the ages of 18 and 55 years who had confirmed and unexplained ischemic or hemorrhagic insults. Alpha-galactosidase enzyme testing was conducted in all suspected cases. Further genetic testing was performed in patients with abnormal enzyme results. Result A total of 51 patients met the inclusion criteria. The mean age was 42 years. All the included patients completed a workup of ischemia or hemorrhage. All cases had no clear etiology of their vascular events. All included patients lacked classic systemic manifestations of Fabry disease. We identified one case of borderline low α-galactosidase A (GLA) enzyme level. However, GLA genetic testing did not reveal any Fabry disease-related mutation. The study did not identify any subject with confirmed Fabry disease. Conclusion In this single-center study, we found that Fabry disease had a low prevalence among Saudi cryptogenic stroke patients who lack other systemic manifestations. Hence, Fabry testing is not generally considered in routine workup related to cryptogenic stroke.

show abstract

“…This is consistent with recent data suggesting that its importance as a cause of early-onset cryptogenic stroke may have been overestimated. 37,38 Our results highlight a major challenge in the use of HTS panels in clinical practice; namely, determining whether a variant is pathogenic or benign. In CADASIL, variant interpretation is aided by the knowledge that all known diseasecausing variants are cysteine-altering.…”

Section: Continuedmentioning

confidence: 85%

How common are single gene mutations as a cause for lacunar stroke?

Tan¹,

Traylor²,

Mégy³

et al. 2019

Neurology

View full text Add to dashboard Cite

ObjectivesTo determine the frequency of rare and pertinent disease-causing variants in small vessel disease (SVD)-associated genes (such as NOTCH3, HTRA1, COL4A1, COL4A2, FOXC1, TREX1, and GLA) in cerebral SVD, we performed targeted gene sequencing in 950 patients with younger-onset apparently sporadic SVD stroke using a targeted sequencing panel.MethodsWe designed a high-throughput sequencing panel to identify variants in 15 genes (7 known SVD genes, 8 SVD-related disorder genes). The panel was used to screen a population of 950 patients with younger-onset (≤70 years) MRI-confirmed SVD stroke, recruited from stroke centers across the United Kingdom. Variants were filtered according to their frequency in control databases, predicted effect, presence in curated variant lists, and combined annotation dependent depletion scores. Whole genome sequencing and genotyping were performed on a subset of patients to provide a direct comparison of techniques. The frequency of known disease-causing and pertinent variants of uncertain significance was calculated.ResultsWe identified previously reported variants in 14 patients (8 cysteine-changing NOTCH3 variants in 11 patients, 2 HTRA1 variants in 2 patients, and 1 missense COL4A1 variant in 1 patient). In addition, we identified 29 variants of uncertain significance in 32 patients.ConclusionRare monogenic variants account for about 1.5% of younger onset lacunar stroke. Most are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy variants, but the second most common gene affected is HTRA1. A high-throughput sequencing technology platform is an efficient, reliable method to screen for such mutations.

show abstract

Prevalence of Fabry Disease and Outcomes in Young Canadian Patients With Cryptogenic Ischemic Cerebrovascular Events

Cited by 24 publications

References 35 publications

Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis

Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis

The Prevalence of Fabry Disease Among Young Cryptogenic Stroke Patients

How common are single gene mutations as a cause for lacunar stroke?

Contact Info

Product

Resources

About