Prevalence of Fabry disease in male dialysis patients: Argentinean screening study

Frabasil, Joaquín; Durand, Consuelo; Sokn, Silvia; Gaggioli, Daniela; Carozza, Patricia; Carabajal, Ricardo; Politei, Juan; Schenone, Andrea

doi:10.1002/jmd2.12035

Cited by 14 publications

(10 citation statements)

References 28 publications

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“…For the same reason, the difference in age at diagnosis between males with the classic form and with a late-onset phenotype is not as large as that observed in other studies. 30,31 The mean enzyme activity is similar between the males of both groups, probably due to the low number of subjects in each group. Lyso-Gb3 levels are much higher in males with the classical form, similarly to other studies.…”

Section: Discussionmentioning

confidence: 89%

Accuracy diagnosis improvement of Fabry disease from dried blood spots: Enzyme activity, lyso‐Gb3 accumulation and GLA gene sequencing

et al. 2021

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The purpose of this study was to examine the applicability of the use of samples in dried blood spot (DBS) for the definitive diagnosis of Fabry disease (FD) in males and females and to compare the diagnostic role of α-galactosidase A activity (α-Gal A), levels of lyso-Gb3 and sequencing of the GLA gene in screening patients with suspected FD. Measurement of α-Gal A activity in suspected FD patients in DBS was made followed by lyso-Gb3 determination and GLA gene sequencing. Of the 2381 subjects analyzed, FD was confirmed in 24 patients. Thirteen different variants were considered like pathogenic, five of which had not been previously described (c.143A > G; c.455A > C; c.487G > T; c.554delA; c.1045_1046insA). None of the patients with normal enzyme activity had FD confirmation. The DBS measurement of α-Gal A was more sensitive than lyso-Gb3 levels in both men and women. Definitive diagnosis of FD from a single DBS is possible, allowing samples to be easily sent from anywhere to the reference laboratory.dried blood spot, Fabry disease, GLA gene, lyso-Gb3, α-galactosidase a activity | INTRODUCTIONFabry disease (FD) is a rare X-linked recessive inherited disorder (OMIM 301500) caused by pathogenic variants in the GLA gene that produce α-galactosidase A (α-Gal A) deficiency. This results in an accumulation of globotriaosylceramide (Gb3) and its deacylated derivative lyso-Gb3 inside of lysosomes, leading to multisystemic disease. 1,2 FD exhibits a wide spectrum of clinical manifestations, from the classic early onset form to the milder later-onset phenotype. Male patients with the classic form develop acroparesthesias, neuropathic pain, corneal opacity (cornea verticillata), angiokeratomas and/or hypohydrosis in childhood or adolescence. Progressive damage to organs occurs with age, and patients may suffer cardiac, renal, and cerebrovascular complications. On the other hand, male patients with the later-onset form develop organic damage during adulthood, mainly chronic kidney disease, hypertrophic cardiomyopathy, and stroke at young age.Females with FD present a heterogeneous expression of disease, from asymptomatic to severe, depending on random X-chromosomal inactivation. [3][4][5] The determination of α-Gal A activity is usually the first step in the laboratory diagnosis. 6,7 However, it is known that in heterozygous females the enzyme activity could be within the normal range. 2,8 A promising biomarker to improve the diagnosis of FD is lyso-Gb3.There is marked elevation of lyso-Gb3 in dried blood spot (DBS) in patients with classic phenotype and its determination has been shown to be a useful tool in screening patients with suspected FD. 9-11 However, the genetic study of the GLA gene continues to be the gold standard for diagnosis, especially in the case of women. 10 Until now, more

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Section: Discussionmentioning

confidence: 89%

Accuracy diagnosis improvement of Fabry disease from dried blood spots: Enzyme activity, lyso‐Gb3 accumulation and GLA gene sequencing

et al. 2021

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“…Older studies from large international registries reported an incidence of FD among patients on dialysis ranging between 0.016% [19] and 0.018% [29,30]. However, many recent studies demonstrated that the incidence of GLA mutations in patients with ESRD may be significantly higher [11]. Doheny et al [14] collected data from 63 screening studies for a total of 51,363 patients, and they found that, among 36,820 (23,954 Males and 12,866 Females) patients on haemodialysis screened, the incidence of FD was 0.42% for males and 0.68% for females.…”

Section: Discussionmentioning

confidence: 99%

“…Progressive renal impairment is a pervasive clinical manifestation of Fabry disease. Studies on FD screening in a hemodialysis population found a prevalence of FD ranging between 0.02% to 1.2% [ 10 , 11 , 12 , 13 , 14 ]. Usually, the first signs are represented by glomerular hyperfiltration associated with mesangial cell proliferation, and they appear between 10 and 20 years of age in male patients with the classic phenotype [ 5 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Screening for Fabry Disease in Kidney Transplant Recipients: Experience of a Multidisciplinary Team

et al. 2020

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Fabry disease (FD) is a rare cause of end-stage renal disease requiring kidney transplantation. Data on the incidence of unrecognized FD in kidney transplant recipients are scarce and probably underestimated. This study evaluated the incidence of FD in a population of kidney recipients, with a particular focus of the multidisciplinary approach for an early clinical assessment and therapeutic approach. Two hundred sixty-five kidney transplant recipients were screened with a genetic analysis for α-galactosidase A (GLA) mutation, with measurement of α-Gal A enzyme activity and Lyso Gb3 levels. Screening was also extended to relatives of affected patients. Seven patients (2.6%) had a GLA mutation. Two patients had a classic form of FD with Fabry nephropathy. Among the relatives, 15 subjects had a GLA mutation, and two had a Fabry nephropathy. The clinical and diagnostic assessment was completed after a median of 3.2 months, and mean time from diagnosis to treatment was 4.6 months. This study reported a high incidence of unrecognized GLA mutations in kidney transplant recipients. Evaluation and management by a multidisciplinary team allowed for an early diagnosis and treatment, and this would result in a delay in the progression of the disease and, finally, in better long-term outcomes.

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“…Each large-scale screening study with >5000 subjects [51][52][53] found >10 GLA variants. In these studies, the most common variants were p.L415P (classical), p.R363H (late-onset), p.M296I, and p.R112H and found in Argentina [51,68]. Notably, p.M296I has been detected as a late-onset variant in Japan [47,66].…”

Section: High-risk Screening For Fd In Individuals With Renal Manifestationsmentioning

confidence: 99%

High-Risk Screening for Fabry Disease: A Nationwide Study in Japan and Literature Review

et al. 2021

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Fabry disease (FD) is an X-linked inherited disorder caused by mutations in the GLA gene, which encodes the lysosomal enzyme α-galactosidase A (α-Gal A). FD detection in patients at an early stage is essential to achieve sufficient treatment effects, and high-risk screening may be effective. Here, we performed high-risk screening for FD in Japan and showed that peripheral neurological manifestations are important in young patients with FD. Moreover, we reviewed the literature on high-risk screening in patients with renal, cardiac, and central neurological manifestations. Based on the results of this study and review of research abroad, we believe that FD can be detected more effectively by targeting individuals based on age. In recent years, the methods for high-risk screening have been ameliorated, and high-risk screening studies using GLA next-generation sequencing have been conducted. Considering the cost-effectiveness of screening, GLA sequencing should be performed in individuals with reduced α-Gal A activity and females with certain FD manifestations and/or a family history of FD. The findings suggest that family analysis would likely detect FD patients, although GLA sequencing of asymptomatic family members requires adequate genetic counseling.

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Prevalence of Fabry disease in male dialysis patients: Argentinean screening study

Cited by 14 publications

References 28 publications

Accuracy diagnosis improvement of Fabry disease from dried blood spots: Enzyme activity, lyso‐Gb3 accumulation and GLA gene sequencing

Accuracy diagnosis improvement of Fabry disease from dried blood spots: Enzyme activity, lyso‐Gb3 accumulation and GLA gene sequencing

Screening for Fabry Disease in Kidney Transplant Recipients: Experience of a Multidisciplinary Team

High-Risk Screening for Fabry Disease: A Nationwide Study in Japan and Literature Review

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