Nationwide screening for Fabry disease in unselected stroke patients

Tomek, Aleš; Reková, Petra; Schwabová, Jaroslava Paulasová; Olšerová, Anna; Škorňa, Miroslav; Nevšímalová, Miroslava; Šimůnek, Libor; Herzig, Roman; Fafejtová, Štěpánka; Mikulenka, Petr; Táboříková, Alena; Neumann, Jiří; Brzezny, Richard; Sobolová, Helena; Bartoník, Jan; Václavík, Daniel; Vachová, Marta; Bechyně, Karel; Havlíková, Hana; Prax, Tomáš; Šaňák, Daniel; Černíková, Irena; Ondečková, Iva; Procházka, Petr; Rajner, Jan; Škoda, Miroslav; Novák, Jan; Škoda, Ondřej; Bar, Michal; Mikulík, Robert; Dostálová, Gabriela; Linhart, Aleš

doi:10.1371/journal.pone.0260601

Cited by 14 publications

(9 citation statements)

References 23 publications

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“…Index-patients were referred to the Department from other clinics, mainly from cardiology where they had been diagnosed during genetic investigation for cardiomyopathy [ 41 ]; to a lesser extent, from neurologists due to atypical neuropathic pain or migraine, or from nephrologists due to incidental findings in a kidney biopsy. In some countries many of the Fabry patients with first manifestations from a stroke or neuropathic pain would be identified by screening [ 63 , 64 ]. A few countries perform newborn screening [ 65 ], which has resulted in disclosing many variants of unknown significance in the GLA gene and only few patients with classical Fabry disease.…”

Section: Discussionmentioning

confidence: 99%

Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience

et al. 2022

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The lysosomal storage disorder Fabry disease is caused by deficient or absent activity of the GLA gene enzyme α-galactosidase A. In the present study we present the molecular and biochemical data of the Danish Fabry cohort and report 20 years’ (2001–2020) experience in cascade genetic screening at the Danish National Fabry Disease Center. The Danish Fabry cohort consisted of 26 families, 18 index patients (9 males and 9 females, no available data for 8 index-patients) and 97 family members with a pathogenic GLA variant identified by cascade genetic testing (30 males and 67 females). Fourteen patients (5 males and 9 females; mean age of death 47.0 and 64.8 years respectively) died during follow-up. The completeness of the Fabry patient identification in the country has resulted in a cohort of balanced genotypes according to gender (twice number of females compared to males), indicating that the cohort was not biased by referral, and further resulted in earlier diagnosis of the disease by a lower age at diagnosis in family members compared to index-patients (mean age at diagnosis: index-patients 42.2 vs. family members 26.0 years). Six previously unreported disease-causing variants in the GLA gene were discovered. The nationwide screening and registration of Fabry disease families provide a unique possibility to establish a complete cohort of Fabry patients and to advance current knowledge of this inherited rare lysosomal storage disorder.

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Section: Discussionmentioning

confidence: 99%

Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience

et al. 2022

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“…Two (0.2%) patients with lacunar ischemic stroke had a pathogenic variant associated with classical FD. Both patients in whom a pathogenic variant of the GLA gene was detected were younger than 50 years of age; 14 patients (1.4%), had a variant of the GLA gene considered to be benign [30]. Based on these data, we consider it necessary and appropriate to suspect FD in patients with ischemic cryptogenic stroke at the age of 19 to 55 years.…”

Section: Cerebrovascular Disordersmentioning

confidence: 89%

“…Today, pathogenetic treatment of the disease -ERT -is possible. Two different forms of ERT are available: Agalsidase-alpha (Replagal, Takeda) and agalsidase-beta (Fabrazyme, Sanofi Genzyme) [30], [47]. Long-term treatment can slow the progression of the disease, but most patients still develop cardiac, renal, and cerebral complications, and the effectiveness of treatment is also reduced in the later stages of the disease when there are irreversible abnormal changes in vital organs and systems [16].…”

Section: Treatment Of Fdmentioning

confidence: 99%

Neurological Manifestations of Fabry Disease: Literature Review

Григолашвили

Kim

Muratbekova

et al. 2022

Open Access Maced J Med Sci

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BACKGROUND: Fabry disease (FD) or Anderson FD is a hereditary disease belonging to the group of lysosomal storage diseases caused by decreased or absent activity of the enzyme α-galactosidase A. Enzyme deficiency leads to accumulation of glycospholipids in the lysosomes of cells of various organs, including the heart, kidneys, nervous system, and vascular endothelium. The complexity of the diagnosis of FD is due to the variety of its symptoms, the simultaneous involvement of many organs and systems. At present, possible pathogenetic treatment of the disease is enzyme replacement therapy, but its effectiveness is reduced in the later stages of the disease, when there are irreversible abnormal changes in vital organs and systems. In this regard, an urgent task is the early diagnosis of FD. AIM: Determination of neurological manifestations of FD as well as clinical criteria for screening for FD. MATERIALS AND METHODS: We analyzed cohort studies, randomized controlled trials, systematic reviews and meta-analyses, case-control studies, and case series from scientific medical databases: PubMed, Web of Science, Google Scholar in Russian, and English languages. CONCLUSION: The authors found that lesions of the nervous system in FD are detected in more than 80% of patients and can manifest as isolated or combined lesions of both the central and peripheral and autonomic nervous systems.

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“…Forty cohort studies that reported on 211 individuals with the D313Y variation in the GLA gene among 42,723 included participants available for genetic analysis were included in the systematic review and subsequent meta-analysis. Six of the cohorts examined patients with cardiac manifestations (including hypertrophic cardiomyopathy), [6][7][8][9][10][11] 9 were conducted among patients with renal manifestations, [12][13][14][15][16][17][18][19][20] 11 included patients with neurologic manifestations (most commonly stroke but also peripheral nerve manifestations), [21][22][23][24][25][26][27][28][29][30][31] 3 cohorts evaluated patients with a history of juvenile idiopathic arthritis, 32 familial Mediterranean fever, 33 and juvenile systematic lupus erythematosus, 34 6 cohorts included patients with high suspicion of FD or as part of relative-screening of known patients with FD, [35][36][37][38][39][40] and 1 study was conducted using newborn screening in the general population. 41 Four studies were conducted among D313Y-positive patients and presented their demographic and clinical characteristics.…”

Section: Cohort Studiesmentioning

confidence: 99%

D313Y Variant in Fabry Disease

et al. 2022

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Background and Objectives There is accumulating evidence in the literature indicating a strong correlation between Fabry disease (FD) phenotypes and specific sequence variations in the Galactosidase Alpha (GLA) gene. Among them, the potential pathogenicity and clinical relevance of D313Y variation in patients with FD remain debated. Methods We performed a systematic review and meta-analysis of studies reporting D313Y as single occurring variant in the GLA gene and sought to evaluate (1) the prevalence of D313Y variation in different populations with or without clinical manifestations of FD, (2) the clinical FD phenotype in D313Y-positive patients, and (3) the proportion of D313Y-positive patients presenting abnormal laboratory findings (alpha-galactosidase-A deficiency or globotriaosylceramide accumulation). Results Forty cohorts comprising 211 individuals with D313Y variation among 42,723 participants with available GLA gene-sequencing data were included. Patients highly suspected for FD had a higher prevalence of D313Y variation (4.9%, 95% CI 1.6%–9.9%; I2 = 95.5%) compared with the general population (0%, 95% CI 0%–0.1%; I2 = 1.9%; p = 0.004). The prevalence of D313Y variation was 0.6% (95% CI 0.3%–1%; I2 = 74.1%), 0.4% (95% CI 0.2%–0.7%; I2 = 0%), and 0.3% (95% CI 0.2%–0.4%; I2 = 0%) in patients presenting with neurologic, cardiac, or renal manifestations, respectively. D313Y was associated with a milder, late-onset FD phenotype, as indicated by the mean patient age of 51 years (95% CI 44–59; I2 = 94%) and the evidence of alpha-galactosidase A deficiency and globotriaosylceramide accumulation in 26.7% (95% CI 15.3%–40%; I2 = 34%) and 16.2% (95% CI 8%–26.4%; I2 = 35%) of cases, respectively. D313Y-positive patients displayed predominantly neurologic FD manifestations (58.1%, 95% CI 37.7%–77.1%; I2 = 78%), with central and peripheral nervous system (CNS/PNS) involvement noted in 28.2% (95% CI 15.4%–43.2%; I2 = 51%) and 28.5% (95% CI 17.8%–40.5%; I2 = 61%) of cases, respectively. Discussion D313Y variation seems to correlate with an atypical, mild late-onset phenotype with predominantly neurologic FD manifestations. Monitoring for CNS/PNS involvement is thus paramount to identify D313Y-positive patients with latent or early-FD pathology, which may qualify for enzyme-replacement therapy or chaperone treatment.

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Nationwide screening for Fabry disease in unselected stroke patients

Cited by 14 publications

References 23 publications

Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience

Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience

Neurological Manifestations of Fabry Disease: Literature Review

D313Y Variant in Fabry Disease

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