Advances in analytical mass spectrometry to improve screening for inherited metabolic diseases

Röschinger, Wulf; Olgemöller, Bernhard; Fingerhut, Ralph; Liebl, Bernhard; Roscher, Adelbert A.

doi:10.1007/s00431-003-1356-y

Cited by 40 publications

(34 citation statements)

References 68 publications

(46 reference statements)

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“…Mass spectrometric assays revolutionized the diagnosis of inherited metabolic disorders, a development co-pioneered in the late 1990s by Adelbert Roscher (Röschinger et al, 2003). This and similar pilot projects around the world taught the diagnostics community some crucial lessons.…”

Section: Technological Advances Paved the Way Into Clinical Applicationsmentioning

confidence: 99%

“…Furthermore, it has been proven for many disorders that multiparametric biomarkers reduce biological noise in the data by internal normalization as well as improve diagnostic sensitivity and specificity. Subsequently, it led to a marked reduction of healthcare costs (Röschinger et al, 2003;Weinberger., 2008).…”

Section: Technological Advances Paved the Way Into Clinical Applicationsmentioning

confidence: 99%

See 1 more Smart Citation

Targeted Metabolomics for Clinical Biomarker Discovery in Multifactorial Diseases

Lundin¹,

Modre-Osprian²,

Weinberger³

2011

Advances in the Study of Genetic Disorders

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Section: Technological Advances Paved the Way Into Clinical Applicationsmentioning

confidence: 99%

Section: Technological Advances Paved the Way Into Clinical Applicationsmentioning

confidence: 99%

Targeted Metabolomics for Clinical Biomarker Discovery in Multifactorial Diseases

Lundin¹,

Modre-Osprian²,

Weinberger³

2011

Advances in the Study of Genetic Disorders

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“…Many metabolic conditions appear to be identifiable with relatively little cost 69,70 and a small sample of blood. However, there is insufficient literature on the clinical application at this time to judge its appropriateness in the evaluation of the child with DD/MR.…”

Section: Metabolic Studiesmentioning

confidence: 99%

“…Because the technology is used for newborn screening programs, the clinical utility in other settings, such as the evaluation of children who might be clinically symptomatic, is being discussed. 69,71 Studies addressing the optimal metabolic evaluation of patients with DD/MR are needed.…”

Section: Metabolic Studiesmentioning

confidence: 99%

Clinical Genetic Evaluation of the Child With Mental Retardation or Developmental Delays

Moeschler¹,

Shevell²

2006

Pediatrics

235

184

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This clinical report describes the clinical genetic evaluation of the child with developmental delays or mental retardation. The purpose of this report is to describe the optimal clinical genetics diagnostic evaluation to assist pediatricians in providing a medical home for children with developmental delays or mental retardation and their families. The literature supports the benefit of expert clinical judgment by a consulting clinical geneticist in the diagnostic evaluation. However, it is recognized that local factors may preclude this particular option. No single approach to the diagnostic process is supported by the literature. This report addresses the diagnostic importance of clinical history, 3-generation family history, dysmorphologic examination, neurologic examination, chromosome analysis (≥650 bands), fragile X molecular genetic testing, fluorescence in situ hybridization studies for subtelomere chromosome rearrangements, molecular genetic testing for typical and atypical presentations of known syndromes, computed tomography and/or magnetic resonance brain imaging, and targeted studies for metabolic disorders.

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“…Targeted MS analyses with higher sensitivity are currently utilized to address these shortcomings (1,2); however, these studies often only analyze a small list of proteins identified as biologically significant. While targeted MS measurements are increasingly common in clinical applications (3,4), the limited number of proteins they examine does not necessarily reflect the biodiversity across a population, making broad untargeted measurements essential in developing individual disease metrics for diagnosis (5). As the future of medicine proceeds toward a personal profiling approach (6,7), the potential for robust high throughput clinical measurements based upon MS is highly attractive, though only if its deficiencies can be addressed.…”

mentioning

confidence: 99%

Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry

Baker

Burnum-Johnson

Jacobs

et al. 2014

Molecular & Cellular Proteomics

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Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is a crucial direction for the field of medicine. While MS-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new instrumental platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry separations with liquid chromatography and MS to dramatically increase measurement sensitivity and throughput, further enabling future high throughput To date pre-clinical and clinical applications of MS-based proteomic techniques analyzing complex biofluids have fallen short of expectations, largely due to deficiencies in both analytical sensitivity and throughput. These deficiencies result in measurements typically failing to confidently detect and quantify proteins at moderate to low concentrations, or not providing sufficient sample analysis throughput for statistical relevance. Targeted MS analyses with higher sensitivity are currently utilized to address these shortcomings (1, 2); however, these studies often only analyze a small list of proteins identified as biologically significant. While targeted MS measurements are increasingly common in clinical applications (3, 4), the limited number of proteins they examine does not necessarily reflect the biodiversity across a population, making broad untargeted measurements essential in developing individual disease metrics for diagnosis (5). As the future of medicine proceeds toward a personal profiling approach (6, 7), the potential for robust high throughput clinical measurements based upon MS is highly attractive, though only if its deficiencies can be addressed. MSAn initial step in attaining broad untargeted measurements that increasingly retain the benefits of targeted analyses exploits technological advances such as faster separations, more effective ion sources, detectors with greater dynamic range, and MS measurements with both higher resolution and accuracy. Advanced liquid-phase separations have already

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Advances in analytical mass spectrometry to improve screening for inherited metabolic diseases

Abstract: This overview aims to describe only current new developments in clinically most relevant applications, in particular with focus on low molecular weight compounds.

Cited by 40 publications

References 68 publications

Targeted Metabolomics for Clinical Biomarker Discovery in Multifactorial Diseases

Targeted Metabolomics for Clinical Biomarker Discovery in Multifactorial Diseases

Clinical Genetic Evaluation of the Child With Mental Retardation or Developmental Delays

Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry

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