High‐Risk Screening for Fabry Disease: Analysis by Tandem Mass Spectrometry of Globotriaosylceramide (Gb 3 ) in Urine Collected on Filter Paper

2017 ◽  
Vol 93 (1) ◽  
Author(s):  
Christiane Auray‐Blais ◽  
Pamela Lavoie ◽  
Michel Boutin ◽  
Mona Abaoui
Keyword(s):  
Mass Spectrometry ◽  
High Risk ◽  
Tandem Mass Spectrometry ◽  
Fabry Disease ◽  
Filter Paper ◽  
Tandem Mass ◽  
Risk Screening ◽  
Disease Analysis ◽  
High Risk Screening

scholarly journals Rapid diagnosis of MCAD deficiency: quantitative analysis of octanoylcarnitine and other acylcarnitines in newborn blood spots by tandem mass spectrometry

1997 ◽  
Vol 43 (11) ◽  
pp. 2106-2113 ◽  
Author(s):  
Donald H Chace ◽  
Steven L Hillman ◽  
Johan L K Van Hove ◽  
Edwin W Naylor
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Chain Length ◽  
Filter Paper ◽  
Tandem Mass ◽  
Mcad Deficiency ◽  
Medium Chain ◽  
Blood Spots ◽  
Medium Chain Length

Abstract We report the application of tandem mass spectrometry to prospective newborn screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. MCAD deficiency is diagnosed from dried blood spots on filter paper cards from newborns on the basis of the increase of medium chain length acylcarnitines identified by isotope dilution mass spectrometry methods. A robust and accurate semiautomated method for the analysis of medium chain length acylcarnitines as their butyl esters was developed and validated. Quantitative data from the analyses of 113 randomly collected filter paper blood spots from healthy newborns showed low concentrations of medium chain length acylcarnitines such as octanoylcarnitine. The maximum concentration of octanoylcarnitine was 0.22 μmol/L, with the majority being at or below the detection limit. In all 16 blood spots from newborns with confirmed MCAD deficiency, octanoylcarnitine was highly increased [median 8.4 μmol/L (range 3.1–28.3 μmol/L)], allowing easy detection. The concentration of octanoylcarnitine was significantly higher in these 16 newborns (<3 days of age) than in 16 older patients (ages 8 days to 7 years) with MCAD deficiency (median 1.57 μmol/L, range 0.33–4.4). The combined experience of prospective newborn screening in Pennsylvania and North Carolina has shown a disease frequency for MCAD deficiency of 1 in 17 706. No false-positive and no known false-negative results have been found. A validated method now exists for prospective newborn screening for MCAD deficiency.

scholarly journals Rapid Screening of High-Risk Patients for Disorders of Purine and Pyrimidine Metabolism Using HPLC-Electrospray Tandem Mass Spectrometry of Liquid Urine or Urine-soaked Filter Paper Strips

2000 ◽  
Vol 46 (4) ◽  
pp. 445-452 ◽  
Author(s):  
Tetsuya Ito ◽  
André B P van Kuilenburg ◽  
Albert H Bootsma ◽  
Anja J Haasnoot ◽  
Arno van Cruchten ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Filter Paper ◽  
Screening Method ◽  
Urine Samples ◽  
Rapid Screening ◽  
Specific Method ◽  
Tandem Mass ◽  
Pyrimidine Metabolism ◽  
Inherited Disorders

Abstract Background: A rapid and specific screening method for patients at risk of inherited disorders of purine and pyrimidine metabolism is desirable because symptoms are varied and nonspecific. The aim of this study was to develop a rapid and specific method for screening with use of liquid urine samples or urine-soaked filter paper strips. Methods: Reverse-phase HPLC was combined with electrospray ionization (ESI), tandem mass spectrometry (MS/MS), and detection performed by multiple reaction monitoring. Transitions and instrument settings were established for 17 purines or pyrimidines. Stable-isotope-labeled reference compounds were used as internal standards when available. Results: Total analysis time of this method was 15 min, approximately one-third that of conventional HPLC with ultraviolet detection. Recoveries were 96–107% in urine with added analyte, with two exceptions (hypoxanthine, 64%; xanthine, 79%), and 89–110% in urine-soaked filter paper strips, with three exceptions (hypoxanthine, 65%; xanthine, 77%; 5-hydroxymethyluracil, 80%). The expected abnormalities were easily found in samples from patients with purine nucleoside phosphorylase deficiency, ornithine transcarbamylase deficiency, molybdenum cofactor deficiency, adenylosuccinase deficiency, or dihydropyrimidine dehydrogenase deficiency. Conclusions: HPLC-ESI MS/MS of urine allows rapid screening for disorders of purine and pyrimidine metabolism. The filter paper strips offer the advantage of easy collection, transport, and storage of the urine samples.

Urinary biomarker investigation in children with Fabry disease using tandem mass spectrometry

2015 ◽  
Vol 438 ◽  
pp. 195-204 ◽  
Author(s):  
Christiane Auray-Blais ◽  
Catherine-Marie Blais ◽  
Uma Ramaswami ◽  
Michel Boutin ◽  
Dominique P. Germain ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Fabry Disease ◽  
Tandem Mass ◽  
Urinary Biomarker

7. An efficient high-risk screening protocol for Fabry disease

2009 ◽  
Vol 96 (2) ◽  
pp. S13 ◽  
Author(s):  
Christiane Auray-Blais ◽  
David S. Millington ◽  
Sarah P. Young ◽  
Joe T.R. Clarke ◽  
Schiffmann Raphael
Keyword(s):  
High Risk ◽  
Fabry Disease ◽  
Risk Screening ◽  
Screening Protocol ◽  
High Risk Screening

scholarly journals Defects in Pyrimidine Degradation Identified by HPLC-Electrospray Tandem Mass Spectrometry of Urine Specimens or Urine-soaked Filter Paper Strips

2000 ◽  
Vol 46 (12) ◽  
pp. 1916-1922 ◽  
Author(s):  
Henk van Lenthe ◽  
André B P van Kuilenburg ◽  
Tetsuya Ito ◽  
Albert H Bootsma ◽  
Arno van Cruchten ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Electrospray Ionization ◽  
Filter Paper ◽  
Degradation Products ◽  
Degradation Pathway ◽  
Urine Samples ◽  
Tandem Mass ◽  
Pyrimidine Degradation ◽  
Ionization Tandem Mass Spectrometry

Abstract Background: Urinary concentrations of thymine, uracil, and their degradation products are useful indicators of deficiencies of enzymes of the pyrimidine degradation pathway. We describe a rapid, specific method to measure these concentrations to detect inborn errors of pyrimidine metabolism. Methods: We used urine or urine-soaked filter-paper strips as samples and measured thymine, uracil, and their degradation products dihydrothymine, dihydrouracil, N-carbamyl-β-aminoisobutyric acid, and N-carbamyl-β-alanine. Reversed-phase HPLC was combined with electrospray ionization tandem mass spectrometry, and detection was performed by multiple-reaction monitoring. Stable-isotope-labeled reference compounds were used as internal standards. Results: All pyrimidine degradation products could be measured in one analytical run of 15 min. Detection limits were 0.4–4 μmol/L. The intraassay imprecision (CV) of urine samples with added compounds was 1.3–12% for liquid urines and 1.0–10% for filter-paper extracts of the urines. The interassay imprecision (CV) was 3–11% (100–200 μmol/L). Recoveries were 89–99% at 100–200 μmol/L and 95–106% at 1 mmol/L in liquid urines, and 93–103% at 100–200 μmol/L and 100–106% at 1 mmol/L in filter-paper samples. Correct identifications of deficiencies of the pyrimidine-degrading enzymes were readily made with urine samples from patients with known defects. Conclusions: HPLC with electrospray ionization tandem mass spectrometry allows rapid testing for disorders of the pyrimidine degradation pathway, and filter-paper samples allow easy collection, transport, and storage of urine samples.

Sign in / Sign up

Export Citation Format

Share Document