Fabry disease: enzymatic diagnosis in dried blood spots on filter paper

Chamoles, N.; Blanco, Mariana; Gaggioli, Daniela

doi:10.1016/s0009-8981(01)00478-8

Cited by 285 publications

(277 citation statements)

References 3 publications

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“…Measurement of aGAL A activity was based on a technique involving a dried blood spot sampled on filter paper (DBS) as described by Chamoles et al (2001). To validate this technique in our laboratory setting, we performed an analysis of 50 control samples (nonnephrology, non-ICU, non-hematology, non-pediatric).…”

Section: Methodsmentioning

confidence: 99%

Questioning the Pathogenic Role of the GLA p.Ala143Thr “Mutation” in Fabry Disease: Implications for Screening Studies and ERT

et al. 2012

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Fabry disease is an X-linked inborn error of glycosphingolipid metabolism caused by quantitative or qualitative defects in the lysosomal enzyme alfa-Galactosidase A (aGAL A), ultimately resulting in vital organ dysfunction. Mainly the kidneys, the heart, and the central nervous system are involved. While the classical phenotype of Fabry disease is readily recognizable, screening studies have identified clinical variants. Here, we report the phenotype associated with the GLA p.Ala143Thr (c.427G>A) mutation in 12 patients aged 42-83 years. None of the patients had classical Fabry signs or symptoms as angiokeratoma, hypohidrosis, acroparesthesia, or cornea verticillata. Possible Fabry manifestations were renal failure (5/12), stroke (7/12), and left ventricular hypertrophy (5/12), but these were not necessarily attributable to the p.Ala143Thr mutation, as a cardiac biopsy in one female and left ventricular hypertrophy and kidney biopsies in two males with renal failure and microalbuminuria lacked Gb-3 deposits. The literature data on this mutation as well as data collected in the Fabry Outcome Survey (FOS) database confirm these findings. The association of renal failure, stroke, and left ventricular hypertrophy with this mutation could be the result of selection bias, as most patients were detected in screening studies.We conclude that care should be taken with attribution of vital organ dysfunction to GLA sequence alterations. In case of the p.Ala143Thr mutation, and possibly also other mutations associated with an attenuated phenotype, diagnostic tools such as biopsy and imaging should critically evaluate the relation of end-organ failure with Fabry disease, as this has important consequences for enzyme replacement therapy.

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Section: Methodsmentioning

confidence: 99%

Questioning the Pathogenic Role of the GLA p.Ala143Thr “Mutation” in Fabry Disease: Implications for Screening Studies and ERT

et al. 2012

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“…Analytical assays on DBS for b-galactosidase, total hexosaminidase, a-galactosidase A, a-L-iduronidase, b-glucosidase, and chitotriosidase were based on the protocols proposed by Chamoles et al (2001aChamoles et al ( , 2001bChamoles et al ( , 2002 and Civallero et al (2006). The analysis of a-glucosidase was performed according to a standardized methodology described by Kallwass et al (2007) and Li et al (2004).…”

Section: Sample Collection For the Controls And Patients In The Studymentioning

confidence: 99%

“…It consists in the enzymatic analysis of dried blood spots (DBS) collected on filter paper ( Fig. 1) (Chamoles et al 2001a(Chamoles et al , 2001bNiizawa et al 2005;Civallero et al 2006;M€ uller et al 2010). This methodology facilitates the packing and shipment of samples because it does not require strict refrigeration and eases the collection of samples for analysis at reference testing centers, allowing the study of high-risk populations without regard to their geographical location.…”

Section: Introductionmentioning

confidence: 99%

Selective Screening for Lysosomal Storage Diseases with Dried Blood Spots Collected on Filter Paper in 4,700 High-Risk Colombian Subjects

Uribe

Giugliani

2013

JIMD Reports

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Lysosomal storage disorders (LSDs) are a very heterogeneous group of hereditary disorders. The diagnostic process usually involves complex sampling, processing, testing, and validation procedures, performed by specialized laboratories only, which causes great limitations in reaching a diagnosis for patients affected by these diseases.There are few studies about LSDs in Colombia. The diagnostic limitations often make medical practitioners disregard the possibility of these disorders while diagnosing their patients. The current study documents the results of a 7-year screening in high-risk patients, aimed to detect LSDs using dried blood spots (DBS) collected on filter paper, with a micromethodology that facilitates diagnosis even with a large number of samples.The activities of a-galactosidase A, a glucosidase, a-Liduronidase, arylsulfatase B, b-galactosidase, b-glucosidase, total hexosaminidase, iduronate sulfatase, and chitotriosidase were analyzed in high-risk patients for lysosomal disease. The catalytic activity was evaluated with fluoro-

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“…For instance, MPS I, II and VI share many clinical features called 'MPS-like' phenotype. This phenotype includes, among others, coarse facial features, hepatosplenomegaly, joint and skeletal dysplasia (dysostosis multiplex, dwarfism, claw-like hand), cardiorespiratory problems, and vision and hearing impairment (Chamoles et al 2001b;Muenzer 2011). In addition, patients with mucolipidosis (ML) II (I-cell disease) and III (pseudo-Hurler polydystrophy) (Van Hoof 1974) may also show a phenotype similar to that of patients with MPS.…”

Section: Introductionmentioning

confidence: 99%

Dried Blood Spots Allow Targeted Screening to Diagnose Mucopolysaccharidosis and Mucolipidosis

Cobos¹,

Steglich²,

Santer³

et al. 2014

JIMD Reports

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Background: As patients with different types of mucopolysaccharidosis (MPS) and mucolipidosis (ML) may present with overlapping clinical features -including coarse face, hepatosplenomegaly, bone dysplasia and claw-hand deformities, collectively also called 'MPS-like phenotype', enzymatic and/or molecular genetic analyses are indispensable for accurate diagnosis and applying specific therapy. In this prospective study, we screened patients with symptoms compatible with MPS for MPS I, II (males) and VI.Methods: Dried blood spots/specimens (DBS) were collected from 200 patients with an MPS-like phenotype and analysed for activities of a-iduronidase (IDUA), iduronate-2-sulphatase (IDS), and arylsulphatase B (ARSB), the enzymes deficient in mucopolysaccharidosis (MPS) type I, II and VI, respectively. For the samples with pathologic enzyme activity, mutational analysis was carried out using the same DBS.Results: Based on enzymatic analysis of 200 DBS samples, a total of 45 (22.5%) showed low activity; 17 for MPS I (8.5%), 11 for MPS II (5.5%) and 9 for MPS VI (4.5%). Enzyme activities were suggestive for ML II/III in 8 (4.0%) cases. For 41 (91.1%) samples, DNA could be extracted from the filter paper. Mutations were identified in 11 (64.7%), 11 (100%), 9 (100%) and 5 (62.5%) patients putatively diagnosed biochemically with MPS I, II, VI, and ML II/III, respectively.Conclusions: DBS enzymatic analysis can be used to diagnose MPS/ML. Initial results should be confirmed by a second enzyme assay and/or by molecular genetic testing. Given the advantages of DBS over other sample types in terms of ease of collection, storage and transportation, DBS are particularly useful for screening patients with an MPS-like phenotype in regions lacking specialised laboratories. In order to ascertain the diagnosis in a large number of cases, patients should be assessed in parallel for at least MPS I, II and VI.

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Fabry disease: enzymatic diagnosis in dried blood spots on filter paper

Cited by 285 publications

References 3 publications

Questioning the Pathogenic Role of the GLA p.Ala143Thr “Mutation” in Fabry Disease: Implications for Screening Studies and ERT

Questioning the Pathogenic Role of the GLA p.Ala143Thr “Mutation” in Fabry Disease: Implications for Screening Studies and ERT

Selective Screening for Lysosomal Storage Diseases with Dried Blood Spots Collected on Filter Paper in 4,700 High-Risk Colombian Subjects

Dried Blood Spots Allow Targeted Screening to Diagnose Mucopolysaccharidosis and Mucolipidosis

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