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Christiane Auray-blais - One of the best experts on this subject based on the ideXlab platform.

  • High-Risk Screening for Fabry disease in a Canadian cohort of chronic kidney disease patients.
    Clinica chimica acta; international journal of clinical chemistry, 2019
    Co-Authors: Christiane Auray-blais, Pamela Lavoie, Michel Boutin, Mona Abaoui, Anne-marie Côté, Ayub Akbari, Adeera Levin, Fabrice Mac-way, Joe T.r. Clarke
    Abstract:

    Abstract Background Fabry disease is an X-linked lysosomal storage disorder with a Highly heterogeneous clinical presentation. This complex disease is caused by a deficient activity of the enzyme α-galactosidase A, which is involved in the catabolism of glycosphingolipids. The prevalence of Fabry disease is underestimated, due to the presence of atypical variants. High-Risk Screening protocols are particularly relevant for this disease due to the availability of treatments, such as enzyme replacement and chaperone therapies. As kidney manifestations are present in the majority of male and many female patients with Fabry disease, a High-Risk Screening protocol was performed for patients with chronic kidney disease of unknown etiology. Methods Recruitment of 397 participants took place in four centers across Canada from 2011 to 2017. Globotriaosylceramide (Gb3) was analyzed in dried urine spots by liquid chromatography/tandem mass spectrometry followed by globotriaosylsphingosine (lyso-Gb3) on the repeat analysis. Results The collection and shipment of urine specimens on filter paper resulted in easier handling/shipment and significant cost-saving. No Fabry patients were detected in this study. Conclusions Increased concentrations of urinary Gb3 were observed in 13.6% of patients with chronic kidney disease suggesting that chronic kidney disease or other comorbidities might be associated with increased urinary Gb3 concentrations.

  • High-Risk Screening for Fabry disease in chronic kidney disease patients
    Molecular Genetics and Metabolism, 2019
    Co-Authors: Pamela Lavoie, Michel Boutin, Mona Abaoui, Anne-marie Côté, Ayub Akbari, Adeera Levin, Fabrice Mac-way, Christiane Auray-blais
    Abstract:

    Fabry disease is a multisystemic, X-linked lysosomal storage disorder caused by a deficit of the enzyme alpha-galactosidase A which leads to the accumulation of glycosphingolipids in tissues and biological fluids. The clinical presentation is heterogeneous with many atypical variants, leading to an underestimated prevalence. Enzyme replacement therapy and chaperone therapy are some of the treatments offered. Since renal dysfunction is a common manifestation of Fabry disease, our group elaborated a High-Risk Screening protocol for patients with chronic kidney disease of unknown etiology. Recruitment of participants took place in four centers across Canada from 2011 to 2017. Participants provided a urine specimen collected on filter paper at their first visit for globotriaosylceramide (Gb3) analysis. If abnormal, a liquid urine specimen was collected for an additional Gb3 and globotriaosylsphingosine (lyso-Gb3) and related analogue analyses. All biomarker analyses were performed by liquid chromatography/tandem mass spectrometry. If an abnormal Gb3 or lyso-Gb3 and related analogue result was obtained upon the 2nd analysis, the measurement of α-galactosidase A activity was requested in males and a mutation analysis in females. A total of 402 patients were recruited. Fifty-three patients (13.2%) had an abnormal Gb3 result on the first analysis. Of these, 50 patients (94.3%) provided a liquid urine specimen for retest, but unfortunately 2 patients were lost to follow-up and one died. Seven patients (14%) still had an abnormal result upon their second urine analysis. Of these latter patients, 3 had passed away when enzyme activity testing was requested. The remaining four patients had normal enzyme activity or mutation analysis. In conclusion, no Fabry patients were detected in this study. Having done 13% retests, this might indicate that urinary Gb3 is not specific enough for High-Risk Screening of Fabry patients having chronic kidney disease. Nevertheless, larger cohorts might be necessary to draw definite conclusions.

  • Current Protocols in Human Genetics - High-Risk Screening for Fabry Disease: Analysis by Tandem Mass Spectrometry of Globotriaosylceramide (Gb3 ) in Urine Collected on Filter Paper.
    Current protocols in human genetics, 2017
    Co-Authors: Christiane Auray-blais, Pamela Lavoie, Michel Boutin, Mona Abaoui
    Abstract:

    Fabry disease is a complex, panethnic lysosomal storage disorder. It is characterized by the accumulation of glycosphingolipids in tissues, organs, the vascular endothelium, and biological fluids. The reported incidence in different populations is quite variable, ranging from 1:1400 to 1:117,000. Its complexity lies in the marked genotypic and phenotypic heterogeneity. Despite the fact that it is an X-linked disease, more than 600 mutations affect both males and females. In fact, some females may be affected as severely as males. The purpose of this protocol is to focus on the High-Risk Screening of patients who might have Fabry disease using a simple, rapid, non-invasive High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for urinary globotriaosylceramide (Gb3 ) analysis. Urine filter paper samples are easily collected at home by patients and sent by regular mail. This method has been successfully used for High-Risk Screening of patients with ophthalmologic manifestations and in an on-going study for High-Risk Screening of Fabry disease in patients with chronic kidney diseases. © 2017 by John Wiley & Sons, Inc.

  • Proposed High-Risk Screening protocol for Fabry disease in patients with renal and vascular disease
    Journal of Inherited Metabolic Disease, 2009
    Co-Authors: Christiane Auray-blais, D. S. Millington, S. P. Young, J. T. R. Clarke, R. Schiffmann
    Abstract:

    Fabry disease is a complex, multisystemic and clinically heterogeneous disease with prominent urinary excretion of globotriaosylceramide (Gb_3), the principal substrate of the deficient enzyme, α-galactosidase A. Some measure of specific treatment is possible with enzyme replacement therapy, which can be applied safely and effectively to Fabry patients. Incidence estimations of Fabry disease vary widely from 1:55 000 to 1:3000 male births. The true incidence is likely to be Higher than originally thought, owing to the existence of milder variants of the disease. The main complications of Fabry disease are a 100-fold increased Risk of ischaemic stroke, cardiac disease, a wide variety of arrhythmias, valvular dysfunction and cardiac vascular disease, as well as progressive renal failure usually associated with significant proteinuria. These clinical manifestations are non-specific and are often mistaken for symptoms of other disorders, thus complicating the confirmation of diagnosis. Other clinical features of the disease are often absent (angiokeratoma), subtle (corneal opacities and hypohidrosis), or unaccompanied by specific physical findings (acroparaesthesias) indicating the true nature of the underlying disease. We propose the hypothesis that α-galactosidase A deficiency is a modifiable cardiovascular Risk factor in the general population. This hypothesis may be tested by a non-invasive High-Risk Screening protocol for Fabry patients with ischaemic strokes and a variety of cardiac, and renal complications. These patients would benefit from diagnosis, appropriate treatment, follow-up and surveillance. Early detection of Fabry patients would also benefit affected relatives, many of whom do not have a clear diagnosis of their clinical condition.

Mona Abaoui - One of the best experts on this subject based on the ideXlab platform.

  • High-Risk Screening for Fabry disease in a Canadian cohort of chronic kidney disease patients.
    Clinica chimica acta; international journal of clinical chemistry, 2019
    Co-Authors: Christiane Auray-blais, Pamela Lavoie, Michel Boutin, Mona Abaoui, Anne-marie Côté, Ayub Akbari, Adeera Levin, Fabrice Mac-way, Joe T.r. Clarke
    Abstract:

    Abstract Background Fabry disease is an X-linked lysosomal storage disorder with a Highly heterogeneous clinical presentation. This complex disease is caused by a deficient activity of the enzyme α-galactosidase A, which is involved in the catabolism of glycosphingolipids. The prevalence of Fabry disease is underestimated, due to the presence of atypical variants. High-Risk Screening protocols are particularly relevant for this disease due to the availability of treatments, such as enzyme replacement and chaperone therapies. As kidney manifestations are present in the majority of male and many female patients with Fabry disease, a High-Risk Screening protocol was performed for patients with chronic kidney disease of unknown etiology. Methods Recruitment of 397 participants took place in four centers across Canada from 2011 to 2017. Globotriaosylceramide (Gb3) was analyzed in dried urine spots by liquid chromatography/tandem mass spectrometry followed by globotriaosylsphingosine (lyso-Gb3) on the repeat analysis. Results The collection and shipment of urine specimens on filter paper resulted in easier handling/shipment and significant cost-saving. No Fabry patients were detected in this study. Conclusions Increased concentrations of urinary Gb3 were observed in 13.6% of patients with chronic kidney disease suggesting that chronic kidney disease or other comorbidities might be associated with increased urinary Gb3 concentrations.

  • High-Risk Screening for Fabry disease in chronic kidney disease patients
    Molecular Genetics and Metabolism, 2019
    Co-Authors: Pamela Lavoie, Michel Boutin, Mona Abaoui, Anne-marie Côté, Ayub Akbari, Adeera Levin, Fabrice Mac-way, Christiane Auray-blais
    Abstract:

    Fabry disease is a multisystemic, X-linked lysosomal storage disorder caused by a deficit of the enzyme alpha-galactosidase A which leads to the accumulation of glycosphingolipids in tissues and biological fluids. The clinical presentation is heterogeneous with many atypical variants, leading to an underestimated prevalence. Enzyme replacement therapy and chaperone therapy are some of the treatments offered. Since renal dysfunction is a common manifestation of Fabry disease, our group elaborated a High-Risk Screening protocol for patients with chronic kidney disease of unknown etiology. Recruitment of participants took place in four centers across Canada from 2011 to 2017. Participants provided a urine specimen collected on filter paper at their first visit for globotriaosylceramide (Gb3) analysis. If abnormal, a liquid urine specimen was collected for an additional Gb3 and globotriaosylsphingosine (lyso-Gb3) and related analogue analyses. All biomarker analyses were performed by liquid chromatography/tandem mass spectrometry. If an abnormal Gb3 or lyso-Gb3 and related analogue result was obtained upon the 2nd analysis, the measurement of α-galactosidase A activity was requested in males and a mutation analysis in females. A total of 402 patients were recruited. Fifty-three patients (13.2%) had an abnormal Gb3 result on the first analysis. Of these, 50 patients (94.3%) provided a liquid urine specimen for retest, but unfortunately 2 patients were lost to follow-up and one died. Seven patients (14%) still had an abnormal result upon their second urine analysis. Of these latter patients, 3 had passed away when enzyme activity testing was requested. The remaining four patients had normal enzyme activity or mutation analysis. In conclusion, no Fabry patients were detected in this study. Having done 13% retests, this might indicate that urinary Gb3 is not specific enough for High-Risk Screening of Fabry patients having chronic kidney disease. Nevertheless, larger cohorts might be necessary to draw definite conclusions.

  • Current Protocols in Human Genetics - High-Risk Screening for Fabry Disease: Analysis by Tandem Mass Spectrometry of Globotriaosylceramide (Gb3 ) in Urine Collected on Filter Paper.
    Current protocols in human genetics, 2017
    Co-Authors: Christiane Auray-blais, Pamela Lavoie, Michel Boutin, Mona Abaoui
    Abstract:

    Fabry disease is a complex, panethnic lysosomal storage disorder. It is characterized by the accumulation of glycosphingolipids in tissues, organs, the vascular endothelium, and biological fluids. The reported incidence in different populations is quite variable, ranging from 1:1400 to 1:117,000. Its complexity lies in the marked genotypic and phenotypic heterogeneity. Despite the fact that it is an X-linked disease, more than 600 mutations affect both males and females. In fact, some females may be affected as severely as males. The purpose of this protocol is to focus on the High-Risk Screening of patients who might have Fabry disease using a simple, rapid, non-invasive High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for urinary globotriaosylceramide (Gb3 ) analysis. Urine filter paper samples are easily collected at home by patients and sent by regular mail. This method has been successfully used for High-Risk Screening of patients with ophthalmologic manifestations and in an on-going study for High-Risk Screening of Fabry disease in patients with chronic kidney diseases. © 2017 by John Wiley & Sons, Inc.

Knut Borch-johnsen - One of the best experts on this subject based on the ideXlab platform.

  • All-cause mortality and pharmacological treatment intensity following a High Risk Screening program for diabetes. A 6.6 year follow-up of the ADDITION study, Denmark.
    Primary care diabetes, 2012
    Co-Authors: Torsten Lauritzen, Annelli Sandbæk, Anders Helles Carlsen, Knut Borch-johnsen
    Abstract:

    Abstract Aim To study all-cause mortality and pharmacological treatment intensity in relation to baseline glucose metabolism and HbA1c following High Risk Screening for diabetes in primary care. Methods Persons aged 40–69 years (N = 163,185) received mailed diabetes Risk questionnaires. 20,916 persons without diabetes but with High Risk of diabetes were stratified by glucose metabolism (normal glucose tolerance (NGT), dysglycemia (IFG or IGT) or diabetes) and by HbA1c at Screening ( Results HR for all-cause mortality increased with increasing levels of HbA1c at Screening in people with NGT and dysglycemia. In people with screen detected diabetes the opposite relation was found. In people with diabetes redeemed prescription rates for lipid-, blood pressure- and glucose-lowering drugs increased significantly following Screening and prescription rates increased with increasing levels of HbA1c at Screening. The same trend in redeemed prescriptions was seen for people with dysglycemia and NGT, but the absolute rates were significantly lower than those among people with screen detected diabetes. Conclusions This study confirms HbA1c as an independent predictor of all-cause mortality in non-diabetic individuals. A likely explanation for the inverse relation found between all-cause mortality and HbA1c at Screening among those with screen detected diabetes would be that intensive treatment near-normalizes mortality. The small group of people with NGT and HbA1c ≥ 6.5%, who had the Highest all-cause mortality, may benefit from being labelled and treated as having diabetes although this group may have special characteristics not accounted for in this study.

  • Progression from impaired fasting glucose and impaired glucose tolerance to diabetes in a High-Risk Screening programme in general practice: the ADDITION Study, Denmark.
    Diabetologia, 2006
    Co-Authors: Signe S. Rasmussen, Torsten Lauritzen, Charlotte Glümer, A. Sandbaek, Knut Borch-johnsen
    Abstract:

    Aims/hypothesis To estimate the 1-year progression rates from both IFG and IGT to diabetes in individuals identified in a pragmatic diabetes Screening programme in general practice (the ADDITION Study, Denmark [Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care]).

R. Schiffmann - One of the best experts on this subject based on the ideXlab platform.

  • Proposed High-Risk Screening protocol for Fabry disease in patients with renal and vascular disease
    Journal of Inherited Metabolic Disease, 2009
    Co-Authors: Christiane Auray-blais, D. S. Millington, S. P. Young, J. T. R. Clarke, R. Schiffmann
    Abstract:

    Fabry disease is a complex, multisystemic and clinically heterogeneous disease with prominent urinary excretion of globotriaosylceramide (Gb_3), the principal substrate of the deficient enzyme, α-galactosidase A. Some measure of specific treatment is possible with enzyme replacement therapy, which can be applied safely and effectively to Fabry patients. Incidence estimations of Fabry disease vary widely from 1:55 000 to 1:3000 male births. The true incidence is likely to be Higher than originally thought, owing to the existence of milder variants of the disease. The main complications of Fabry disease are a 100-fold increased Risk of ischaemic stroke, cardiac disease, a wide variety of arrhythmias, valvular dysfunction and cardiac vascular disease, as well as progressive renal failure usually associated with significant proteinuria. These clinical manifestations are non-specific and are often mistaken for symptoms of other disorders, thus complicating the confirmation of diagnosis. Other clinical features of the disease are often absent (angiokeratoma), subtle (corneal opacities and hypohidrosis), or unaccompanied by specific physical findings (acroparaesthesias) indicating the true nature of the underlying disease. We propose the hypothesis that α-galactosidase A deficiency is a modifiable cardiovascular Risk factor in the general population. This hypothesis may be tested by a non-invasive High-Risk Screening protocol for Fabry patients with ischaemic strokes and a variety of cardiac, and renal complications. These patients would benefit from diagnosis, appropriate treatment, follow-up and surveillance. Early detection of Fabry patients would also benefit affected relatives, many of whom do not have a clear diagnosis of their clinical condition.

Pamela Lavoie - One of the best experts on this subject based on the ideXlab platform.

  • High-Risk Screening for Fabry disease in a Canadian cohort of chronic kidney disease patients.
    Clinica chimica acta; international journal of clinical chemistry, 2019
    Co-Authors: Christiane Auray-blais, Pamela Lavoie, Michel Boutin, Mona Abaoui, Anne-marie Côté, Ayub Akbari, Adeera Levin, Fabrice Mac-way, Joe T.r. Clarke
    Abstract:

    Abstract Background Fabry disease is an X-linked lysosomal storage disorder with a Highly heterogeneous clinical presentation. This complex disease is caused by a deficient activity of the enzyme α-galactosidase A, which is involved in the catabolism of glycosphingolipids. The prevalence of Fabry disease is underestimated, due to the presence of atypical variants. High-Risk Screening protocols are particularly relevant for this disease due to the availability of treatments, such as enzyme replacement and chaperone therapies. As kidney manifestations are present in the majority of male and many female patients with Fabry disease, a High-Risk Screening protocol was performed for patients with chronic kidney disease of unknown etiology. Methods Recruitment of 397 participants took place in four centers across Canada from 2011 to 2017. Globotriaosylceramide (Gb3) was analyzed in dried urine spots by liquid chromatography/tandem mass spectrometry followed by globotriaosylsphingosine (lyso-Gb3) on the repeat analysis. Results The collection and shipment of urine specimens on filter paper resulted in easier handling/shipment and significant cost-saving. No Fabry patients were detected in this study. Conclusions Increased concentrations of urinary Gb3 were observed in 13.6% of patients with chronic kidney disease suggesting that chronic kidney disease or other comorbidities might be associated with increased urinary Gb3 concentrations.

  • High-Risk Screening for Fabry disease in chronic kidney disease patients
    Molecular Genetics and Metabolism, 2019
    Co-Authors: Pamela Lavoie, Michel Boutin, Mona Abaoui, Anne-marie Côté, Ayub Akbari, Adeera Levin, Fabrice Mac-way, Christiane Auray-blais
    Abstract:

    Fabry disease is a multisystemic, X-linked lysosomal storage disorder caused by a deficit of the enzyme alpha-galactosidase A which leads to the accumulation of glycosphingolipids in tissues and biological fluids. The clinical presentation is heterogeneous with many atypical variants, leading to an underestimated prevalence. Enzyme replacement therapy and chaperone therapy are some of the treatments offered. Since renal dysfunction is a common manifestation of Fabry disease, our group elaborated a High-Risk Screening protocol for patients with chronic kidney disease of unknown etiology. Recruitment of participants took place in four centers across Canada from 2011 to 2017. Participants provided a urine specimen collected on filter paper at their first visit for globotriaosylceramide (Gb3) analysis. If abnormal, a liquid urine specimen was collected for an additional Gb3 and globotriaosylsphingosine (lyso-Gb3) and related analogue analyses. All biomarker analyses were performed by liquid chromatography/tandem mass spectrometry. If an abnormal Gb3 or lyso-Gb3 and related analogue result was obtained upon the 2nd analysis, the measurement of α-galactosidase A activity was requested in males and a mutation analysis in females. A total of 402 patients were recruited. Fifty-three patients (13.2%) had an abnormal Gb3 result on the first analysis. Of these, 50 patients (94.3%) provided a liquid urine specimen for retest, but unfortunately 2 patients were lost to follow-up and one died. Seven patients (14%) still had an abnormal result upon their second urine analysis. Of these latter patients, 3 had passed away when enzyme activity testing was requested. The remaining four patients had normal enzyme activity or mutation analysis. In conclusion, no Fabry patients were detected in this study. Having done 13% retests, this might indicate that urinary Gb3 is not specific enough for High-Risk Screening of Fabry patients having chronic kidney disease. Nevertheless, larger cohorts might be necessary to draw definite conclusions.

  • Current Protocols in Human Genetics - High-Risk Screening for Fabry Disease: Analysis by Tandem Mass Spectrometry of Globotriaosylceramide (Gb3 ) in Urine Collected on Filter Paper.
    Current protocols in human genetics, 2017
    Co-Authors: Christiane Auray-blais, Pamela Lavoie, Michel Boutin, Mona Abaoui
    Abstract:

    Fabry disease is a complex, panethnic lysosomal storage disorder. It is characterized by the accumulation of glycosphingolipids in tissues, organs, the vascular endothelium, and biological fluids. The reported incidence in different populations is quite variable, ranging from 1:1400 to 1:117,000. Its complexity lies in the marked genotypic and phenotypic heterogeneity. Despite the fact that it is an X-linked disease, more than 600 mutations affect both males and females. In fact, some females may be affected as severely as males. The purpose of this protocol is to focus on the High-Risk Screening of patients who might have Fabry disease using a simple, rapid, non-invasive High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for urinary globotriaosylceramide (Gb3 ) analysis. Urine filter paper samples are easily collected at home by patients and sent by regular mail. This method has been successfully used for High-Risk Screening of patients with ophthalmologic manifestations and in an on-going study for High-Risk Screening of Fabry disease in patients with chronic kidney diseases. © 2017 by John Wiley & Sons, Inc.