Detection of blood Gb3 deposits as a new tool for diagnosis and therapy monitoring in patients with classic Fabry disease

Üçeyler, Nurcan; Böttger, J.; Henkel, Lisa; Langjahr, Melissa; Mayer, Christine; Nordbeck, Peter; Wanner, Christoph; Sommer, Claudia

doi:10.1111/joim.12801

Cited by 14 publications

(13 citation statements)

References 24 publications

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“…In human tubular cells, the expression of CD77 increases when the expression of a-Gal A is inhibited in vitro and it is significantly reduced when treated with agalsidase-α [97]. In peripheral blood mononuclear cells (PBMC) of FD patients, Gb3 levels were also significantly increased compared to control subjects [97,98] and they decreased significantly with treatment [99]. Table S1 (Supplementary Materials) lists the above mentioned accumulation biomarkers with the main characteristics.…”

Section: Accumulation Biomarkersmentioning

confidence: 99%

Biomarkers in Fabry Disease. Implications for Clinical Diagnosis and Follow-up

Carnicer-Cáceres

Arranz-Amo

Cea-Arestin

et al. 2021

JCM

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Fabry disease (FD) is a lysosomal storage disorder caused by deficient alpha-galactosidase A activity in the lysosome due to mutations in the GLA gene, resulting in gradual accumulation of globotriaosylceramide and other derivatives in different tissues. Substrate accumulation promotes different pathogenic mechanisms in which several mediators could be implicated, inducing multiorgan lesions, mainly in the kidney, heart and nervous system, resulting in clinical manifestations of the disease. Enzyme replacement therapy was shown to delay disease progression, mainly if initiated early. However, a diagnosis in the early stages represents a clinical challenge, especially in patients with a non-classic phenotype, which prompts the search for biomarkers that help detect and predict the evolution of the disease. We have reviewed the mediators involved in different pathogenic mechanisms that were studied as potential biomarkers and can be easily incorporated into clinical practice. Some accumulation biomarkers seem to be useful to detect non-classic forms of the disease and could even improve diagnosis of female patients. The combination of such biomarkers with some response biomarkers, may be useful for early detection of organ injury. The incorporation of some biomarkers into clinical practice may increase the capacity of detection compared to that currently obtained with the established diagnostic markers and provide more information on the progression and prognosis of the disease.

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Section: Accumulation Biomarkersmentioning

confidence: 99%

Biomarkers in Fabry Disease. Implications for Clinical Diagnosis and Follow-up

Carnicer-Cáceres

Arranz-Amo

Cea-Arestin

et al. 2021

JCM

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“…An interesting approach to detect Gb3 deposits in peripheral blood mononuclear cells (PBMCs)19 represents a low-cost and simple alternative to invasive biopsies. What is more, the Gb3 load in PBMC decreases with long-term ERT and could potentially be used for disease monitoring.…”

Section: Introductionmentioning

confidence: 99%

Hot topics in Fabry disease

Cairns

Müntze

Gernert

et al. 2018

Postgraduate Medical Journal

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Fabry disease is a rare inborn error of the enzyme α-galactosidase (α-Gal) and results in lysosomal substrate accumulation in tissues with a wide range of clinical presentations. The disease has attracted a lot of interest over the last years, in particular since enzyme replacement therapy (ERT) has become widely available in 2001. With rising awareness and rising numbers of (diagnosed) patients, physicians encounter new challenges. Over 900 α-Gal gene mutations are currently known, some with doubtful clinical significance, posing diagnostic and prognostic difficulties for the clinician and a lot of uncertainty for patients. Another challenge are patients who develop neutralising antibodies to ERT, which possibly leads to reduced therapy effectiveness. In this article, we summarise the latest developments in the science community regarding diagnostics and management of this rare lysosomal storage disorder and offer an outlook to future treatments.

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“…Moreover, it is possible that methods for measuring Gb3 accumulation in urine and blood [25,26] and Lyso-Gb3 in blood [27] might be insufficient for some female patients with FD [28]. Individuals are likely to have false-positive results when they harbor nonpathogenic polymorphisms.…”

Section: Methods For High-risk Screeningmentioning

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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Detection of blood Gb3 deposits as a new tool for diagnosis and therapy monitoring in patients with classic Fabry disease

Abstract: Gb3 can be visualized in PBMC and blood smears and can be used as a novel marker for diagnostics, follow-up and treatment control in FD.

Cited by 14 publications

References 24 publications

Biomarkers in Fabry Disease. Implications for Clinical Diagnosis and Follow-up

Biomarkers in Fabry Disease. Implications for Clinical Diagnosis and Follow-up

Hot topics in Fabry disease

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

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