INTRODUCTION: Fabry disease (FD) can be undiagnosed in the context of multiple sclerosis (MS) due to similar clinical and paraclinical features. Our study aimed to determine the prevalence (and the necessity of screening) of FD among patients with possible or definite MS. METHODS: In this prospective monocentric observational study, we included consecutive patients enrolled between May 2017 and May 2019 after the first clinical event suggestive of MS. All patients underwent FD screening using dried blood spots in a stepwise manner combining genetic and enzyme testing. Patients were followed until May 2022. RESULTS: We included 160 patients (73.1% female, mean age 33.9 years). The 2017 revised McDonald's criteria for definite MS were fulfilled by 74 (46.3%) patients at the time of study recruitment and 89 (55.6%) patients after 3-5 years of follow-up. None of the patients had a pathogenic GLA variant, and four (2.5%) had a variant of unknown significance (p.A143T, p.S126G, 2 × p.D313Y). In two of these patients, the intrathecal synthesis of oligoclonal bands was absent, and none had hyperproteinorachia or pleocytosis in cerebrospinal fluid. Detailed examination of FD organ manifestations revealed only discrete ocular and kidney involvement in two patients. CONCLUSION: The prevalence of FD in the population of suspected or definite MS patients does not appear to be high. Our results do not support routine FD screening in all patients with a possible diagnosis of MS, but there is an urgent need to search for red flags and include FD in the differential diagnosis of MS.
- MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- Fabryho nemoc * diagnóza epidemiologie MeSH
- lidé MeSH
- nepoznaná diagnóza MeSH
- prospektivní studie MeSH
- roztroušená skleróza * diagnóza epidemiologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
BACKGROUND: Anderson-Fabry disease (AFD) is an X-linked inherited lysosomal disease caused by a defect in the gene encoding lysosomal enzyme α-galactosidase A (GLA). Atrio-ventricular (AV) nodal conduction defects and sinus node dysfunction are common complications of the disease. It is not fully elucidated how frequently AFD is responsible for acquired AV block or sinus node dysfunction and if some AFD patients could manifest primarily with spontaneous bradycardia in general population. The purpose of study was to evaluate the prevalence of AFD in male patients with implanted permanent pacemaker (PM). METHODS: The prospective multicentric screening in consecutive male patients between 35 and 65 years with implanted PM for acquired third- or second- degree type 2 AV block or symptomatic second- degree type 1 AV block or sinus node dysfunction was performed. RESULTS: A total of 484 patients (mean age 54 ± 12 years at time of PM implantation) were enrolled to the screening in 12 local sites in Czech Republic. Out of all patients, negative result was found in 481 (99%) subjects. In 3 cases, a GLA variant was found, classified as benign: p.Asp313Tyr, p.D313Y). Pathogenic GLA variants (classical or non-classical form) or variants of unclear significance were not detected. CONCLUSION: The prevalence of pathogenic variants causing AFD in a general population sample with implanted permanent PM for AV conduction defects or sinus node dysfunction seems to be low. Our findings do not advocate a routine screening for AFD in all adult males with clinically significant bradycardia.
- MeSH
- atrioventrikulární blokáda * diagnóza epidemiologie terapie MeSH
- bradykardie komplikace terapie MeSH
- dospělí MeSH
- Fabryho nemoc * diagnóza epidemiologie genetika MeSH
- kardiostimulátor * škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- senioři MeSH
- syndrom chorého sinu diagnóza epidemiologie terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The diagnosis of Fabry disease (FD) has relevant implications related to the management. Thus, a clear assignment of GLA variant pathogenicity is crucial. This systematic review and meta-analysis aimed to investigate the prevalence of FD in high-risk populations and newborns and evaluate the impact of different GLA variant classifications on the estimated prevalence of FD. METHODS: We searched the EMBASE and PubMed databases on February 21, 2023. Observational studies evaluating the prevalence of FD and reporting the identified GLA variants were included. GLA variants were re-evaluated for their pathogenicity significance using the American College of Medical Genetics and Genomics criteria and the ClinVar database. The pooled prevalence of FD among different settings was calculated. The study was registered on PROSPERO (CRD42023401663) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. RESULTS: Of the 3941 studies identified, 110 met the inclusion criteria. The pooled prevalence of FD was significantly different according to the clinical setting and criteria used for the pathogenicity assessment. Using the American College of Medical Genetics and Genomics criteria, the pooled prevalence was 1.2% in patients with left ventricular hypertrophy/hypertrophic cardiomyopathy (26 studies; 10 080 patients screened), 0.3% in end-stage renal disease/chronic kidney disease (38 studies; 62 050 patients screened), 0.7% in stroke (25 studies; 15 295 patients screened), 0.7% in cardiac conduction disturbance requiring pacemaker (3 studies; 1033 patients screened), 1.0% in small-fiber neuropathy (3 studies; 904 patients screened), and 0.01% in newborns (15 studies; 11 108 793 newborns screened). The pooled prevalence was different if the GLA variants were assessed using the ClinVar database, and most patients with a discrepancy in the pathogenicity assignment carried 1 of the following variants: p.A143T, p.D313Y, and p.E66Q. CONCLUSIONS: This systematic review and meta-analysis describe the prevalence of FD among newborns and high-risk populations, highlighting the need for a periodic reassessment of the GLA variants in the context of recent clinical, biochemical, and histological data. REGISTRATION: URL: https://crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42023401663.
- MeSH
- alfa-galaktosidasa genetika MeSH
- cévní mozková příhoda * MeSH
- Fabryho nemoc * diagnóza epidemiologie genetika MeSH
- hypertrofie levé komory srdeční MeSH
- lidé MeSH
- novorozenec MeSH
- prevalence MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
Parapelvické cysty ledvin se nachází v oblasti ledvinné pánvičky. Jsou většinou asymptomatické a zjištěné náhodně na ultrazvuku ledvin, výjimečně mohou vést k symptomům, jako jsou bolesti v bedrech při obstrukci vývodných močových cest, k hematurii nebo infekci. K jejich definitivní diagnóze je někdy nutné provést CT vyšetření s kontrastní látkou a vylučovací fází. Parapelvické cysty mohou být součástí dědičných polycystických chorob ledvin. Dále jejich výskyt byl častěji popsán u Fabryho choroby.
- Klíčová slova
- parapelvické cysty ledvin,
- MeSH
- cystická onemocnění ledvin * diagnostické zobrazování genetika patologie MeSH
- diferenciální diagnóza MeSH
- Fabryho nemoc diagnóza patologie MeSH
- lidé MeSH
- nemoci ledvin diagnostické zobrazování patologie vrozené MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Pegunigalsidase alfa is a novel, PEGylated α-galactosidase-A enzyme-replacement therapy approved in the EU and US to treat patients with Fabry disease (FD). OBJECTIVE/METHODS: BRIDGE is a phase 3 open-label, switch-over study designed to assess safety and efficacy of 12 months of pegunigalsidase alfa (1 mg/kg every 2 weeks) treatment in adults with FD who had been previously treated with agalsidase alfa (0.2 mg/kg every 2 weeks) for ≥ 2 years. RESULTS: Twenty-seven patients were screened; 22 met eligibility criteria; and 20 (13 men, 7 women) completed the study. Pegunigalsidase alfa was well-tolerated, with 97% of treatment-emergent adverse events (TEAEs) being of mild or moderate severity. The incidence of treatment-related TEAEs was low, with 2 (9%) discontinuations due to TEAEs. Five patients (23%) reported infusion-related reactions. Overall mean (SD; n = 22) baseline estimated glomerular filtration rate (eGFR) was 82.5 (23.4) mL/min/1.73 m2 and plasma lyso-Gb3 level was 38.3 (41.2) nmol/L (men: 49.7 [45.8] nmol/L; women: 13.8 [6.1] nmol/L). Before switching to pegunigalsidase alfa, mean (standard error [SE]) annualized eGFR slope was - 5.90 (1.34) mL/min/1.73 m2/year; 12 months post-switch, the mean eGFR slope was - 1.19 (1.77) mL/min/1.73 m2/year; and mean plasma lyso-Gb3 reduced by 31%. Seven (35%) out of 20 patients were positive for pegunigalsidase alfa antidrug antibodies (ADAs) at ≥ 1 study timepoint, two of whom had pre-existing ADAs at baseline. Mean (SE) changes in eGFR slope for ADA-positive and ADA-negative patients were + 5.47 (3.03) and + 4.29 (3.15) mL/min/1.73 m2/year, respectively, suggesting no negative impact of anti-pegunigalsidase alfa ADAs on eGFR slope. CONCLUSION: Pegunigalsidase alfa may offer a safe and effective treatment option for patients with FD, including those previously treated with agalsidase alfa. TRN: NCT03018730. Date of registration: January 2017.
- MeSH
- alfa-galaktosidasa terapeutické užití MeSH
- dospělí MeSH
- enzymová substituční terapie metody MeSH
- Fabryho nemoc * farmakoterapie MeSH
- izoenzymy škodlivé účinky MeSH
- lidé MeSH
- protilátky terapeutické užití MeSH
- rekombinantní proteiny terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Úvod: Fabryho choroba je vzácné dědičné střádavé onemocnění postihující různé orgány včetně vestibulokochleárního aparátu a může vést k předčasné hypakuzi a tinnitu. Časná a správná dia gnostika Fabryho choroby je důležitá pro zahájení terapie. Cíl práce: Cílem práce bylo zhodnocení hypakuze u pacientů s Fabryho chorobou, porovnání rozdílů mezi muži a ženami a mezi jednotlivými fenotypy. Materiál a metodika: Byla provedena retrospektivní studie u pacientů vyšetřených v naší ambulanci v rozmezí let 2016–2020 tónovou audiometrií na 7 frekvencích (0,125–8 kHz). Pacientům byly zhodnoceny audiometrické křivky na pravém a levém uchu, spočítány průměrné procentuální ztráty dle Fowlera na pravém a levém uchu a celkové, dále byly spočítány průměrné procentuální ztráty dle Fowlera u jednotlivých fenotypů Fabryho choroby. Závěrem jsme porovnali vývoj hypakuze v čase u pacientů vyšetřených vícekrát. Výsledky: Bylo vyšetřeno 121 pacientů (55 mužů a 66 žen) s prokázanou Fabryho chorobou. Ženy měly percepční hypakuzi vpravo ve 48,5 % a vlevo v 50 % případů. Kombinovanou hypakuzi mělo 1,5 % žen. Muži měli percepční hypakuzi vpravo v 63,6 % a vlevo v 65,5 %. Kombinovanou hypakuzi mělo 1,8 % mužů. Celkové průměrné procentuální ztráty dle Fowlera byly u žen 8,8 % a u mužů 14,8 %. Ženy s klasickým fenotypem měly statisticky významně horší sluch než ženy s ostatními fenotypy. U mužů nebyl žádný fenotyp statisticky významně horší. Závěr: Pacienti s Fabryho chorobu v našem souboru měli nejčastěji percepční hypakuzi. Hypakuze u mužů s Fabryho chorobou byla statisticky významně horší než u žen.
Introduction: Fabry disease (FD) is a rare hereditary lysosomal storage disease aff ecting diff erent organs, including the cochlea-vestibular system. It can lead to premature hearing loss and tinnitus. Early and correct dia gnosis of FD is important with a view of available therapy. Purpose: The aim of this study is to evaluate the degree of hearing loss in patients with FD. Additionally, to compare diff erences between male and female patients as well as the diff erences of types of FD in patients with diff erent phenotypes. Methods: This is a retrospective study of patients that had been examined in our out-patient offi ce in the years 2016–2020. We used 7-tone pure-tone audiometry (0,125–8 kHz). We compared audiograms of patients right and left ear, calculated average Fowler percentage of hearing loss on left ear, right ear and combined. We compared combined Fowler percentage of hearing loss in diff erent types of FD based on the disease phenotype. Moreover, we compared the progress of hearing loss in time in patients that were examined in our offi ce more than once. Results: We examined 121 patients (55 male, 66 female) with dia gnosed FD. Female patients exhibited 48.5% hearing loss in the right ear and 50% in the left ear. Mixed hearing loss occurred in 1.5% of females in the group. We observed sensorineural hearing loss in 63.6% in the right ear and 65.5% in the left ear within male patients. Mixed hearing loss appeared in 1.8% of male patients. Combined mean Fowler percentage of hearing loss in females was 8.8 % and in males 14.8 %. Female patients with the classic type of FD had signifi cantly worse hearing than females with any other type of FD. This was not observed in the male group. Conclusion: Patients with FD in our group of patients had mostly sensorineural hearing loss. Hearing loss of male patients with FD was signifi cantly worse than females.
- MeSH
- audiometrie MeSH
- dospělí MeSH
- Fabryho nemoc * diagnóza genetika terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- nedoslýchavost * diagnóza MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
OBJECTIVES: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with variable phenotypes, including neurological symptoms. These can be influenced by vascular impairment. Extracranial and transcranial vascular sonography is an effective and noninvasive method for measuring arterial structures and blood flow. The study aims to investigate cerebrovascular phenotype characteristics in FD patients compared to controls using neurosonology. METHODS: This is a single-center, cross-sectional study of 130 subjects-65 patients (38 females), with genetically confirmed FD, and 65 sex- and age-matched controls. Using ultrasonography, we measured structural and hemodynamic parameters, including distal common carotid artery intima-media thickness, inner vertebral artery diameter, resting blood flow velocity, pulsatility index, and cerebral vasoreactivity (CVR) in the middle cerebral artery. To assess differences between FD and controls and to identify factors influencing investigated outcomes, unadjusted and adjusted regression analyses were performed. RESULTS: In comparison to sex- and age-matched controls, FD patients displayed significantly increased carotid artery intima-media thickness (observed FD 0.69 ± 0.13 mm versus controls 0.63 ± 0.12 mm; Padj = .0014), vertebral artery diameter (observed FD 3.59 ± 0.35 mm versus controls 3.38 ± 0.33 mm; Padj = .0002), middle cerebral artery pulsatility index (observed FD 0.98 ± 0.19 versus controls 0.87 ± 0.11; Padj < .0001), and significantly decreased CVR (observed FD 1.21 ± 0.49 versus controls 1.35 ± 0.38; Padj = .0409), when adjusted by age, BMI, and sex. Additionally, FD patients had significantly more variable CVR (0.48 ± 0.25 versus 0.21 ± 0.14; Padj < .0001). CONCLUSIONS: Our results suggest the presence of multiple vascular abnormalities and changes in hemodynamic parameters of cerebral arteries in patients with FD.
- MeSH
- Fabryho nemoc * diagnostické zobrazování MeSH
- hemodynamika fyziologie MeSH
- intimomediální šíře tepenné stěny MeSH
- lidé MeSH
- mozkový krevní oběh fyziologie MeSH
- průřezové studie MeSH
- rychlost toku krve fyziologie MeSH
- ultrasonografie dopplerovská transkraniální metody MeSH
- ultrasonografie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Fabry disease (FD, α-galactosidase A deficiency) is a rare, progressive, complex lysosomal storage disorder affecting multiple organ systems with a diverse spectrum of clinical phenotypes, particularly among female patients. Knowledge of its clinical course was still limited in 2001 when FD-specific therapies first became available and the Fabry Registry (NCT00196742; sponsor: Sanofi) was initiated as a global observational study. The Fabry Registry has now been operational for over 20 years, overseen by expert Boards of Advisors, and has collected real-world demographic and longitudinal clinical data from more than 8000 individuals with FD. Leveraging the accumulating evidence base, multidisciplinary collaborations have resulted in the creation of 32 peer-reviewed scientific publications, which have contributed to the greatly expanded knowledge on the onset and progression of FD, its clinical management, the role of sex and genetics, the outcomes of enzyme replacement therapy with agalsidase beta, and prognostic factors. We review how the Fabry Registry has evolved from its inception to become the largest global source of real-world FD patient data, and how the generated scientific evidence has helped to better inform the medical community, individuals living with FD, patient organizations, and other stakeholders. The patient-centered Fabry Registry fosters collaborative research partnerships with the overarching goal of optimizing the clinical management of patients with FD and is well positioned to add to its past achievements.
- MeSH
- alfa-galaktosidasa genetika terapeutické užití MeSH
- enzymová substituční terapie metody MeSH
- Fabryho nemoc * farmakoterapie epidemiologie genetika MeSH
- fenotyp MeSH
- lidé MeSH
- péče orientovaná na pacienta MeSH
- pozorovací studie jako téma MeSH
- registrace MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- alfa-galaktosidasa MeSH
- Fabryho nemoc * diagnostické zobrazování MeSH
- jod * MeSH
- lidé MeSH
- myokard MeSH
- počítačová rentgenová tomografie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
AIMS: Fabry disease (FD) is a multisystemic lysosomal storage disorder caused by a defect in the alpha-galactosidase A gene that manifests as a phenocopy of hypertrophic cardiomyopathy. We assessed the echocardiographic 3D left ventricular (LV) strain of patients with FD in relation to heart failure severity using natriuretic peptides, the presence of a cardiovascular magnetic resonance (CMR) late gadolinium enhancement scar, and long-term prognosis. METHODS AND RESULTS: 3D echocardiography was feasible in 75/99 patients with FD [aged 47 ± 14 years, 44% males, LV ejection fraction (EF) 65 ± 6% and 51% with hypertrophy or concentric remodelling of the LV]. Long-term prognosis (death, heart failure decompensation, or cardiovascular hospitalization) was assessed over a median follow-up of 3.1 years. A stronger correlation was observed for N-terminal pro-brain natriuretic peptide levels with 3D LV global longitudinal strain (GLS, r = -0.49, P < 0.0001) than with 3D LV global circumferential strain (GCS, r = -0.38, P < 0.001) or 3D LVEF (r = -0.25, P = 0.036). Individuals with posterolateral scar on CMR had lower posterolateral 3D circumferential strain (CS; P = 0.009). 3D LV-GLS was associated with long-term prognosis [adjusted hazard ratio 0.85 (confidence interval 0.75-0.95), P = 0.004], while 3D LV-GCS and 3D LVEF were not (P = 0.284 and P = 0.324). CONCLUSION: 3D LV-GLS is associated with both heart failure severity measured by natriuretic peptide levels and long-term prognosis. Decreased posterolateral 3D CS reflects typical posterolateral scarring in FD. Where feasible, 3D-strain echocardiography can be used for a comprehensive mechanical assessment of the LV in patients with FD.
- MeSH
- dysfunkce levé srdeční komory * diagnostické zobrazování etiologie MeSH
- echokardiografie trojrozměrná * metody MeSH
- echokardiografie metody MeSH
- Fabryho nemoc * komplikace diagnostické zobrazování MeSH
- funkce levé komory srdeční MeSH
- gadolinium MeSH
- jizva diagnostické zobrazování MeSH
- kontrastní látky MeSH
- lidé MeSH
- prognóza MeSH
- reprodukovatelnost výsledků MeSH
- srdeční selhání * diagnostické zobrazování etiologie MeSH
- tepový objem MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH