暂无摘要。

UNASSIGNED: The aim of this study is to explore the expression of inflammatory cytokines (ICs) in Fabry disease (FD), the correlation between ICs and FD phenotypes, and the impact of enzyme replacement therapy (ERT) on IC expression.
UNASSIGNED: We recruited 67 FD patients and 44 healthy controls (HCs) and detected concentrations of the following ICs: interferon-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, IL-17F, IL-22, tumor necrosis factor (TNF)-α, and TNF-β. We also analyzed the impact of ERT on IC expression in FD patients and the relationship between IC expression and sex, genotype, phenotype, disease burden, and biomarkers.
UNASSIGNED: Most ICs were significantly higher in FD patients than in HCs. A number of ICs were positively correlated with clinical aspects, including disease burden (Mainz Severity Score Index [MSSI]) and cardiac and renal markers. IL-8 was higher in the high MSSI (P-adj=0.026*) than in the low MSSI.
UNASSIGNED: ICs were upregulated in FD patients, indicating the role of the innate immune process in FD etiology. ERT ameliorated FD-related inflammatory activation, at least to some extent. IC expression was positively correlated with disease burden and clinical markers in FD. Our findings indicated that the inflammatory pathway may be a promising therapeutic target for FD.

OBJECTIVE: Left ventricular hypertrophy (LVH) is frequently detected via echocardiography in individuals with Fabry disease (FD), sometimes leading to confusion with hypertrophic cardiomyopathy (HCM) of other aetiologies. Considering this diagnosis challenge, FD should be included in the list of differential diagnosis for patients presenting with LVH. To address this concern, we conducted a prospective screening study in China, using dried blood spot (DBS) testing, to evaluate patients with unexplained LVH.
METHODS: Our study was designed as a nationwide, multicentre prospective investigation. A total of 1015 patients from 55 different centres who were diagnosed with LVH by echocardiography were screened in the study from September 2022 to December 2023. Demographic information, biochemistry data, echocardiography parameters and clinical observations were meticulously collected from all participants. The DBS method was used to assess α-galactosidase A (α-Gal A) activity in males and both α-Gal A and globotriaosylsphingosine (lyso-Gb3) levels in females.
RESULTS: The final screening population included 906 patients (589 males, 65%) with LVH, characterized by a mean maximal myocardial thickness of 14.8 ± 4.6 mm and an average age of 56.9 ± 17.2 years. In total, 43 patients (38 males, 5 females) exhibited low α-Gal A activity measurement (<2.2 μmol/L), while 21 patients (10 males, 11 females) presented low α-Gal A activity or elevated lyso-Gb3 levels (>1.1 ng/mL). Among these patients, eight individuals (7 males and 1 female) were genetically confirmed to harbour pathogenic GLA mutations, resulting in a total prevalence of 0.88%. Compared with patients without FD, patients with FD tended to have proteinuria (75% vs. 21.2%, P = 0.001), family history of HCM (37.5% vs. 2.3%, P < 0.01) and neuropathic pain (37.5% vs. 4.4%, P < 0.01) but lower systolic blood pressure (118.5 ± 12.5 vs. 143.3 ± 29.3 mmHg, P = 0.017). Five mutations were previously recognized as associated with FD while the remaining two, p.Asp313Val (c.938A>T) and c.547+3A>G, were deemed potentially pathogenic. Subsequent familial validation post-diagnosis identified an additional 14 confirmed cases.
CONCLUSIONS: This pioneering screening study for FD among Chinese patients with unexplained LVH using DBS measurement, revealed an FD detection rate of 0.88%. Our findings confirmed that the combined measurement of lyso-Gb3 and α-Gal A activity is beneficial for primary screening of FD in patients with LVH. Given the availability of efficacious therapies and the value of cascade screening in extended families, early detection of FD in LVH patients is clinically important.

UNASSIGNED: Fabry disease is a rare X-linked lysosomal storage disorder caused by α-galactosidase A (α-Gal A) deficiency. Reduced or absent enzyme activity causes progressive lysosomal accumulation of globotriaosylceramide (Lyso-Gb3) in various cells throughout the body to trigger inflammation and fibrosis.
UNASSIGNED: We present the first familial case of Fabry Disease in North Macedonia identified based on clinical manifestations and confirmed through enzyme, biomarker, and genetic tests. The index case in the family was a 45-year-old male undergoing hemodialysis therapy. He has had chronic burning uncontrolled limb pain since childhood, intermittent abdominal cramps, anhidrosis, and hypertension. The constellation of clinical presentations accompanied by similar symptoms in close family members prompted the enzyme, biomarker, and genetic analyses for Fabry disease. Genetic testing identified a known pathogenic GLA missense variant c.443G>A or p.(Ser148Asn) in the hemizygous state. Subsequent family studies allowed identification of another hemizygous male and five heterozygous female carriers affected by this X-linked disorder.
UNASSIGNED: We report identification of the first familial case of Fabry disease in North Macedonia and describe the phenotype associated with the Ser148Asn GLA variant. Greater awareness of this rare disease linked to continuous medical education is crucial for timely diagnosis and treatment.

Anderson-Fabry disease (AFD) is a genetic lysosomal storage disorder caused by mutations in the α-galactosidase A gene, leading to impaired lysosomal function and resulting in both macrovascular and microvascular alterations. AFD patients often exhibit increased intima-media thickness (IMT) and reduced flow-mediated dilation (FMD), indicating non-atherosclerotic arterial thickening and the potential for cardiovascular events. Nailfold capillaroscopy, a non-invasive diagnostic tool, has shown potential in diagnosing and monitoring microcirculatory disorders in AFD, despite limited research. This study evaluates nailfold capillaroscopy findings in AFD patients, exploring correlations with GLA gene variant subgroups (associated with classical or late-onset phenotypes and variants of uncertain significance (VUSs)), and assessing morpho-functional differences between sexes. It aims to determine whether capillaroscopy can assist in the early identification of individuals with multiorgan vascular involvement. A retrospective observational study was conducted with 25 AFD patients from AOUP \"G. Rodolico-San Marco\" in Catania (2020-2023). Patients underwent genetic testing, enzyme activity evaluation, and nailfold capillaroscopy using Horus basic HS 200 videodermatoscopy. Parameters like angiotectonic disorder, vascular areas, capillary density, and intimal thickening were assessed. The study identified significant differences in capillaroscopy findings among patients with different GLA gene variant subgroups. Classic AFD variant patients showed reduced capillary length and signs of erythrocyte aggregation and dilated subpapillary plexus. No correlation was found between enzymatic activity and capillaroscopy parameters. However, Lyso-Gb3 levels were positively correlated with average capillary length (ῤ = 0.453; p = 0.059). Sex-specific differences in capillaroscopy findings were observed in neoangiogenesis and average capillary length, with distinct implications for men and women. This study highlights the potential of nailfold capillaroscopy in the diagnostic process and clinical management of AFD, particularly in relation to specific GLA gene mutations, as a valuable tool for the early diagnosis and monitoring of AFD.

Fabry disease (FD) is an X-linked lysosomal storage disorder which leads to the accumulation of globotriaosylceramide (Gb3) in various organs, including the heart. FD can be subdivided into classic disease resulting from negligible residual enzyme activity and a milder, atypical phenotype with later onset and less severe clinical presentation. The use of multimodality cardiac imaging including echocardiography, cardiac magnetic resonance and nuclear imaging is important for the diagnostic and prognostic evaluation in these patients. There are gaps in the literature regarding the comprehensive description of cardiac findings of FD and its evaluation by multimodality imaging. In this review, we describe the contemporary practices and roles of multimodality cardiac imaging in individuals affected with Fabry disease.

Fabry disease (FD) leads to significant morbidity and mortality, which may indicate accelerated ageing. However, it is still unclear whether there is a relationship between telomere length (TL), a marker of biological ageing, and disease outcome. We aimed to examine the relationship between leukocyte TL (LTL) dynamics and the presence of advanced disease stages and/or late complications of FD, including hypertrophic cardiomyopathy, nephropathy and stroke, both cross-sectionally and longitudinally. DNA was extracted from peripheral blood leukocytes and quantitative PCR was utilized to determine relative LTL in 99 Fabry patients. In the longitudinal analysis, we included 50 patients in whom at least three measurements were performed over a period of 5-10 years. The results showed a significant inverse correlation between LTL and age (ρ = -0.20, p = 0.05). No significant differences in LTL were found between females and males (p = 0.79) or between patients receiving disease-specific therapy and those without (p = 0.34). In a cross-sectional analysis, no association was found between the presence (p = 0.15) or number (p = 0.28) of advanced stages of the disease and/or late complications and LTL. Similarly, in a longitudinal analysis, no difference in LTL dynamics was found regarding the presence (p = 0.16) of advanced stage organ involvement and/or late complications or their number. These findings indicate that LTL dynamics in adulthood may not be a reliable indicator of disease outcomes in Fabry patients. Therefore, LTL may more accurately reflect the disease burden in early life, when TL is primarily determined.

OBJECTIVE: Fabry disease (FD) causes glycosphingolipid accumulation in the vascular endothelium, with predominantly cardiac and renal involvement. Its prevalence in patients with concomitant involvement of these two organs is unknown. The objective of the study was to determine the prevalence of FD in patients with left ventricular hypertrophy and any degree of chronic kidney disease.
METHODS: Patients with ventricular thickness ≥13mm and kidney disease from 29 Spanish hospitals were included. Sociodemographic variables and target organ involvement of FD were collected. Laboratory determinations of EF were carried out, with an enzymatic activity test±genetic test in men and direct genetic test in women.
RESULTS: Eight hundred ninety-eight patients with left ventricular hypertrophy and chronic kidney disease were included. The presence of heart failure and cardiorenal syndrome was common (46.1% and 40.1%). Three patients (2 men and 1 woman) were diagnosed with FD, based on the presence of a pathogenic variant in the GLA gene and classic signs of FD, resulting in a prevalence of 0.33% (CI 95% 0.06-1%). Six patients (0.66%) presented genetic variants of unknown significance, without showing classic signs of FD, while in 13 patients (3.2%) performing the blood test was impossible.
CONCLUSIONS: FD is an important cause of left ventricular hypertrophy and chronic kidney disease. Genetic diagnosis is crucial for avoiding biases and ensuring accurate identification of FD, especially in women. The results support the inclusion of this disease in the differential diagnosis of patients with ventricular hypertrophy ≥13mm and chronic kidney disease.

法布雷病是一种可累及全身多种脏器的罕见病，其中心脏受累是法布雷病患者生活质量下降及死亡的主要原因。本例患者因突发心悸第一次来院，予心电图检查诊断为心房颤动（房颤），行房颤射频消融术，术后长期给予胺碘酮预防复发，1年后患者因活动后胸闷气促再次来院，查体发现患者双下肢轻度水肿，躯干及四肢指尖角质瘤样改变，B型脑钠肽升高，心超及三维斑点标测提示室间隔及左室游离壁轻度增厚，心脏磁共振提示左室游离壁对比剂延迟强化，结合患者幼年期间出现排汗减少，右侧听力减退，考虑法布雷病可能，在完善α半乳糖苷酶A活性和脱乙酰基三己糖酰基鞘脂醇（GL-3）检测及法布雷基因筛查后确诊。患者在停用胺碘酮2周后心衰症状较前缓解，B型脑钠肽下降至正常水平。确诊后患者启动酶替代治疗，3个月治疗后复查心超可见室间隔厚度变薄，脱乙酰基GL-3水平明显下降。.

BACKGROUND: The spectrum of clinical presentation of Fabry disease (FD) in women is broad and challenging. The aim is to evaluate the effectiveness of an alternative screening method for FD in women.
METHODS: A collaborative multicenter cross-sectional study to evaluate the sensitivity and specificity of the combination of two tests (α-GAL enzyme activity assay and lyso-GL3 assay) for the diagnosis of FD in women. We included women with chronic kidney disease (CKD) stages 3 to 5, receiving conservative treatment or on dialysis programs, from different nephrology services in Brazil.
RESULTS: We evaluated 1874 patients that underwent blood collection for α-GAL and lyso-GL3 assays. Isolated decreased α-GAL enzyme activity was found in 64 patients (3.5%), while isolated increased lyso-GL3 levels were found in 67 patients (3.6%), with one patient presenting alterations in both tests. All cases with low α-GAL enzyme activity and/or increased lyso-GL3 levels underwent genetic analysis for FD variants (132 performed GLA genetic test). Low α-GAL enzyme activity had higher sensitivity and specificity to detect FD compared to the other measures (elevated lyso-GL3 alone or both altered). The negative predictive value (NPV) of α-GAL activity was 99%, and the positive predictive value (PPV) was 9.2%. For lyso-GL3 assay, the specificity was 99.7% and the PPV was 2.9%, therefore considered inferior to α-GAL assay. Both assays altered, had higher PPV (100%) and higher NPV (99.7%) considered the best method. We found 7 cases of GLA gene variants found, resulting in an initial prevalence of 0.37% for FD in this sample female population.
CONCLUSIONS: This study contributes to the diagnostic value of the biomarkers α-GAL and lyso-GL3 in the context of FD in women with CKD. The combination of these biomarkers was an effective approach for the diagnosis of the disease, with high PPV and NPV.