Fabry Disease

Desnick, Robert J.

doi:10.1016/b978-0-12-410529-4.00038-3

Cited by 6 publications

(3 citation statements)

References 72 publications

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“…Fabry disease (FD) is a rare X-linked disorder characterized by partial or complete deficiency of the enzyme α-galactosidase A due to mutations in the GLA gene, which leads to lysosomal accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3) and its deacylated metabolite, globotriaosylsphingosine (lyso-Gb3) [1, 2]. The progressive accumulation of these compounds over time causes cellular dysfunction and subsequent damage to vital organs such as the heart, the brain, and the kidneys [1-3].…”

Section: Introductionmentioning

confidence: 99%

Growth Differentiation Factor-15 and Syndecan-1 Are Potential Biomarkers of Cardiac and Renal Involvement in Classical Fabry Disease under Enzyme Replacement Therapy

Gregório¹,

BIAGINI²,

Cunha³

et al. 2022

Kidney Blood Press Res

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Background and aims: Inflammation and endothelial damage play a pivotal role in Fabry disease (FD) manifestations. In daily clinical practice, FD are mainly monitored by traditional biomarkers of target organ injury, such as serum creatinine and proteinuria, which provide no information about inflammation and endothelial damage. Materials and methods: We investigated the serum levels of 3-nitrotyrosine (3-NT), an oxidative stress biomarker, and of growth differentiation factor-15 (GDF-15) and syndecan-1 in classical FD patients on enzyme replacement therapy (ERT) for at least 6 months and their relationship with Fabry-related cardiac and renal manifestations. Results: Fifty-two classical FD patients (37 females) on ERT for 62.0 ± 27.5 months were included in the study. The main clinical manifestations included nephropathy (67.3%) and cardiomyopathy (21.1%). Serum levels of 3-NT, syndecan-1, and GDF-15 were 33.3 (4.8–111.1) nmol/mL, 55.7 (38.8–74.9) ng/mL, and 541.8 (392.2–784.4) pg/mL, respectively. There was a direct correlation between interventricular septal thickness and serum GDF-15 (r=0.59; P<0.001) and syndecan-1(r=0.30, P=0.04). Among kidney parameters, there was a significant correlation between estimated glomerular filtration rate and GDF-15 (r=-0.61; P<0.001), as well as between 24 h proteinuria and syndecan-1 (r=0.28; P=0.04). Serum GDF-15 levels were significantly higher in patients with cardiomyopathy (P=0.03) as well in those with both nephropathy and cardiomyopathy (P=0.02), than in patients without these comorbidities. Serum GDF-15 levels were also significantly higher in patients who started ERT at an older age (≥40 years). In multivariate analysis, syndecan-1, 3-NT, GDF-15, time on ERT and arterial pressure differentiated Fabry patients with both cardiac and renal involvement from those without these manifestations. Conclusions: GDF-15 and syndecan-1 were associated with parameters of cardiac and renal involvement in classic FD patients on ERT. Their potential association with residual risk and disease outcomes should be investigated. Keywords: Fabry disease, enzyme replacement therapy, biomarkers, inflammation, oxidative stress.

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Section: Introductionmentioning

confidence: 99%

Growth Differentiation Factor-15 and Syndecan-1 Are Potential Biomarkers of Cardiac and Renal Involvement in Classical Fabry Disease under Enzyme Replacement Therapy

Gregório¹,

BIAGINI²,

Cunha³

et al. 2022

Kidney Blood Press Res

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“…The enzyme α-Galactosidase (α-Gal) A removes terminal α-galactose residues from glycosphingolipids, including GL-3. Thus, inherited defects of α-Gal lead to the Fabry-Anderson disorder-usually defined as "Fabry disease"-a progressive, multisystemic lysosomal storage disorder, characterized by GL-3 accumulation [3]. Anderson-Fabry (or Anderson-Fabry) is an X-linked disorder caused by mutation of the α-Gal A (α-Gal A) gene (Reference Sequence accession number NG_007119 (NM_000169.3:c.1117G>A), MIM 300644; numbering like [4,5]).…”

Section: Introductionmentioning

confidence: 99%

“…Under the clinical profile, the Fabry disease is characterized by a markedly increased risk of early ischemic disease that is particularly pronounced at the heart and brain levels [3,7]. However, the disease also manifests during infancy or early adolescence through symptoms that reflect the involvement of the peripheral nervous system and kidney function, with the progressive onset of peripheral neuropathy, proteinuria, and overt renal failure [8].…”

Section: Introductionmentioning

confidence: 99%

Effects of agalsidase-β administration on vascular function and blood pressure in familial Anderson–Fabry disease

et al. 2020

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Fabry is an X-linked disorder of glycosphingolipid metabolism that is caused by variants of the GLA gene that codes for α-galactosidase A, leading to lysosomal accumulation of globotriaosylceramide in many cell types. As a result, affected patients manifest with an increased risk of developing ischemic stroke, peripheral neuropathy, cardiac dysfunction, and chronic kidney disease. The protective effects of enzyme replacement therapy (ERT), the milestone in Fabry disease treatment, against globotriaosylceramide (GL-3) accumulation and Fabry disease progression are well known. However, the mechanism of action of ERT is not well understood. Since GL-3 also accumulates in the vascular endothelium, we investigated the effects of agalsidase-β, a recombinant human α-Gal enzyme approved for the treatment of Fabry disease. In this study, vascular function and blood pressure in four adult siblings affected by Fabry disease were evaluated upon agalsidase-β. In all patients, agalsidase-β infusion improves flow-mediated dilation and augmentation index. These changes occurred after the first infusion and were then maintained for the whole period of observation, i.e., 1 year, with more pronounced additional increments in flow-mediated dilation after the second agalsidase-β infusion. Blood pressure was also maintained at optimal levels in all of the patients for the whole period of observation. Our findings show that agalsidase-β administration can improve vascular function in patients suffering from Fabry disease. Changes in flow-mediated dilation and augmentation index persisted for the whole period of observation (1 year), thus suggesting that early substitutive therapy should be promoted in order to protect the cardiovascular system.

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Ocular findings and their correlation with disease severity in Fabry disease in South-East Anatolia

et al. 2023

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Fabry Disease

Cited by 6 publications

References 72 publications

Growth Differentiation Factor-15 and Syndecan-1 Are Potential Biomarkers of Cardiac and Renal Involvement in Classical Fabry Disease under Enzyme Replacement Therapy

Growth Differentiation Factor-15 and Syndecan-1 Are Potential Biomarkers of Cardiac and Renal Involvement in Classical Fabry Disease under Enzyme Replacement Therapy

Effects of agalsidase-β administration on vascular function and blood pressure in familial Anderson–Fabry disease

Ocular findings and their correlation with disease severity in Fabry disease in South-East Anatolia

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