Determination of the lysosomal hydrolase activity in blood collected on filter paper, an alternative to screen high risk populations

Castilhos, Cristina Dickie de; Mezzalira, J. C.; Daitx, Vanessa Vitcoski; Garcia, Cristina da Silva; Andrade, Carina Loureiro; Breier, Ana Carolina; Cé, Jaqueline; Mello, Alexandre Silva de; Coelho, Janice Carneiro

doi:10.1016/j.gene.2013.11.101

Cited by 12 publications

(5 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The α-Gal A activity in DBS has been used for screening purposes and should be followed by enzymatic activity in leukocytes or DNA sequencing to confirm the diagnosis [9]. The efficacy of the applicability of enzymatic activity in DBS as an alternative screening test has been reported [8,[22][23][24]. Fuller and colleagues [25] tested DBS enzyme activity assay in FD hemizygous patients and found a clearly decrease in α-Gal A activity when compared with a control population.…”

Section: Discussionmentioning

confidence: 99%

Correlation between GLA variants and alpha-Galactosidase A profile in dried blood spot: an observational study in Brazilian patients

Varela

Kirsztajn

Motta

et al. 2020

Orphanet J Rare Dis

View full text Add to dashboard Cite

Background: Fabry disease is a rare X-linked inherited disorder caused by deficiency of α-Galactosidase A. Hundreds of mutations and non-coding haplotypes in the GLA gene have been described; however, many are variants of unknown significance, prompting doubts about the diagnosis and treatment. The α-Galactosidase A enzymatic activity in dried blood spot (DBS) samples are widely used for screening purposes; however, even when values below the normal are found, new tests are required to confirm the diagnosis. Here we describe an analysis of GLA variants and their correlation with DBS α-Galactosidase A enzymatic activity in a large Brazilian population with Fabry disease symptoms. Results: We analyzed GLA variants by DNA sequencing of 803 male patients with suspected Fabry disease or belonging to high-risk populations; in 179 individuals, 58 different exonic variants were detected. From these, 50 are variants described as pathogenic and eight described as variants of unknown significance. The other individuals presented complex non-coding haplotypes or had no variants. Interestingly, the enzymatic activity in DBS was different among pathogenic variants and the other genotypes, including variants of unknown significance; the first presented mean of 12% of residual activity, while the others presented levels above 70% of the activity found in healthy controls. Conclusion: The activity of α-Galactosidase A in DBS was markedly reduced in males with known pathogenic variants when compared with subjects presenting variants of unknown significance, non-coding haplotypes, or without variants, indicating a possible non-pathogenic potential of these latter genotypes. These findings bring a better understanding about the biochemical results of α-Galactosidase A in DBS samples, as well as the possible non-pathogenic potential of non-coding haplotypes and variants of unknown significance in GLA gene. These results certainly will help clinicians to decide about the treatment of patients carrying variants in the gene causing this rare but life-threatening disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Correlation between GLA variants and alpha-Galactosidase A profile in dried blood spot: an observational study in Brazilian patients

Varela

Kirsztajn

Motta

et al. 2020

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…As a whole, we propose the Fq method for screening ARSB EA in a wide population screening program, and the SuSiq method for further diagnostic purposes [18]. Our approach can even be extended to ARSB EA analyses in DBS from high risk populations [19]. Most importantly, the incorporation of an internal standard can be extended to other EA measurements with β-MU-derived substrates for the detection of LSD, where blood components play such important quenching effects when using DBS samples.…”

Section: Discussionmentioning

confidence: 99%

Improving arylsulfatase activity determination in dried blood spots: Screening and diagnostic approaches for Maroteaux–Lamy syndrome (MPS VI)

Franco

Pérez

Aranda

et al. 2015

Clinica Chimica Acta

View full text Add to dashboard Cite

“…One of the most popular methods for screening and/or diagnosing MPS VI, or other LSD, uses specific 4-methylumbelliferone (β-MU)-derived synthetic substrates to measure the ARSB EA, where the hydrolysis of the substrate releases fluorescent β-MU 12 . The resulting fluorescence is interpolated in β-MU calibration curves for EA determination.…”

Section: Samples Used For Fluorometric Determinations Of Eamentioning

confidence: 99%

Update on the fluorometric measurement of enzymatic activities for Lysosomal Storage Disorder detection: The example of MPS VI.

Franco¹,

Adamo²,

Mathieu³

et al. 2017

J Rare Dis Res Treat

View full text Add to dashboard Cite

Lysosomal Storage Disorders (LSD) are rare diseases that as a whole have a combined incidence ranging from 1:1500 to 1:7000 live births. One of such diseases is Mucopolysaccharidosis VI (MPS VI), or Maroteaux Lamy Syndrome. MPS VI patients undergo devastating and irreversible skeletal alterations and multisystemic failure as from early childhood due to reduced Arylsulfatse B (ARSB) enzyme activity.Reaching a final diagnosis is not always a short cut path, but rather a yearslong battle against uncertainty and unnecessary medical interventions. Our aim is to contribute from the bench table with different approaches that could serve as alternatives to pre-existing assays for screening and diagnosing MPS VI and other LSD.

show abstract

Determination of the lysosomal hydrolase activity in blood collected on filter paper, an alternative to screen high risk populations

Cited by 12 publications

References 28 publications

Correlation between GLA variants and alpha-Galactosidase A profile in dried blood spot: an observational study in Brazilian patients

Correlation between GLA variants and alpha-Galactosidase A profile in dried blood spot: an observational study in Brazilian patients

Improving arylsulfatase activity determination in dried blood spots: Screening and diagnostic approaches for Maroteaux–Lamy syndrome (MPS VI)

Update on the fluorometric measurement of enzymatic activities for Lysosomal Storage Disorder detection: The example of MPS VI.

Contact Info

Product

Resources

About