A renal variant of Fabry disease: A case with a novel Gal A hemizygote mutation

Mukdsi, Jorge Humberto; Gutiérrez, Silvina; Barrón, Belén; Novoa, P.; Fernandez, S.; Diller, Ana; Torres, Alicia Inés; Formica, Richard N.; Orías, Marcelo

doi:10.5812/nephropathol.8123

Cited by 8 publications

(6 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another OS publication reported that one of three patients had detectable proteinuria at baseline which resolved during treatment [80] (Supplementary Table 8). Five CRs with agalsidase beta showed an improvement in proteinuria [86,88,92,95,96], whereas one showed no change [87], and one a worsening [85].…”

Section: Resultsmentioning

confidence: 99%

The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: A systematic literature review by a European panel of experts

Germain

Elliott

Falissard

et al. 2019

Molecular Genetics and Metabolism Reports

153

View full text Add to dashboard Cite

BackgroundEnzyme replacement therapy (ERT) with recombinant human α-galactosidase has been available for the treatment of Fabry disease since 2001 in Europe and 2003 in the USA. Treatment outcomes with ERT are dependent on baseline patient characteristics, and published data are derived from heterogeneous study populations.MethodsWe conducted a comprehensive systematic literature review of all original articles on ERT in the treatment of Fabry disease published up until January 2017. This article presents the findings in adult male patients.ResultsClinical evidence for the efficacy of ERT in adult male patients was available from 166 publications including 36 clinical trial publications. ERT significantly decreases globotriaosylceramide levels in plasma, urine, and in different kidney, heart, and skin cell types, slows the decline in estimated glomerular filtration rate, and reduces/stabilizes left ventricular mass and cardiac wall thickness. ERT also improves nervous system, gastrointestinal, pain, and quality of life outcomes.ConclusionsERT is a disease-specific treatment for patients with Fabry disease that may provide clinical benefits on several outcomes and organ systems. Better outcomes may be observed when treatment is started at an early age prior to the development of organ damage such as chronic kidney disease or cardiac fibrosis. Consolidated evidence suggests a dose effect. Data described in male patients, together with female and paediatric data, informs clinical practice and therapeutic goals for individualized treatment.

show abstract

Section: Resultsmentioning

confidence: 99%

The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: A systematic literature review by a European panel of experts

Germain

Elliott

Falissard

et al. 2019

Molecular Genetics and Metabolism Reports

153

View full text Add to dashboard Cite

show abstract

“…While mutation p.(Cys174Arg) is reportedly associated with classic FD [25], p.(Cys174Gly) is still classified as a single nucleotide polymorphism (SNP) at the Short Genetic Variations database (dbSNP) of the National Center for Biotechnology Information (NCBI; National Library of Medicine, Bethesda, MD, USA; http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=181562693, last accessed on August 1, 2014]. However, GLA p.(Cys174Gly) has recently been identified in a patient presenting with an unusual late-onset renal variant of FD [26], raising doubts about its clinical benignity [27]. …”

Section: Introductionmentioning

confidence: 99%

The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: Data from individual patients and family studies

Ferreira

Ortíz

Germain

et al. 2015

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

Summary Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue – GLA p.(Arg118Cys) –, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands’ close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease, since the allelic frequency in stroke patients was 0.0087 (p=0.0185 vs the general population). The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for “rare” condition.

show abstract

“…The Cys174Arg [115,147] mutation was expected to be a pathogenic mutation. GLA Cys174Gly were recently identified in a patient presenting with an unusual late-onset renal variant of Fabry disease [148], suggesting that this mutation was not clinically benign [149]. In addition, the GLA Arg118Cys variant was recently reported in large case-finding studies in different European populations [150,151,152,153] and Brazil [154] among patients with stroke, left ventricular hypertrophy, or on chronic dialysis.…”

Section: Fabry Diseasementioning

confidence: 99%

Genetic Factors of Cerebral Small Vessel Disease and Their Potential Clinical Outcome

Giau

Bagyinszky

Youn

et al. 2019

IJMS

View full text Add to dashboard Cite

Cerebral small vessel diseases (SVD) have been causally correlated with ischemic strokes, leading to cognitive decline and vascular dementia. Neuroimaging and molecular genetic tests could improve diagnostic accuracy in patients with potential SVD. Several types of monogenic, hereditary cerebral SVD have been identified: cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL), hereditary diffuse leukoencephalopathy with spheroids (HDLS), COL4A1/2-related disorders, and Fabry disease. These disorders can be distinguished based on their genetics, pathological and imaging findings, clinical manifestation, and diagnosis. Genetic studies of sporadic cerebral SVD have demonstrated a high degree of heritability, particularly among patients with young-onset stroke. Common genetic variants in monogenic disease may contribute to pathological progress in several cerebral SVD subtypes, revealing distinct genetic mechanisms in different subtype of SVD. Hence, genetic molecular analysis should be used as the final gold standard of diagnosis. The purpose of this review was to summarize the recent discoveries made surrounding the genetics of cerebral SVD and their clinical significance, to provide new insights into the pathogenesis of cerebral SVD, and to highlight the possible convergence of disease mechanisms in monogenic and sporadic cerebral SVD.

show abstract

A renal variant of Fabry disease: A case with a novel Gal A hemizygote mutation

Cited by 8 publications

References 9 publications

The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: A systematic literature review by a European panel of experts

The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: A systematic literature review by a European panel of experts

The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: Data from individual patients and family studies

Genetic Factors of Cerebral Small Vessel Disease and Their Potential Clinical Outcome

Contact Info

Product

Resources

About