Mass spectrometry in clinical chemistry: the case of newborn screening

Marca, Giancarlo la

doi:10.1016/j.jpba.2014.03.047

Cited by 56 publications

(54 citation statements)

References 53 publications

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“…DBS samples are routinely collected from all neonates born in the Italian regions of Tuscany and Umbria (about 40000/year) for NBS (12). In order to have the highest possible sensitivity, a 2 nd TT for free methylmalonic and 3-OH-propionic acid has been performed since 2007 if first screen C3 value is ≥ 3.3 µmol/L.…”

Section: Methodsmentioning

confidence: 99%

Heptadecanoylcarnitine (C17) a novel candidate biomarker for newborn screening of propionic and methylmalonic acidemias

Malvagia

Haynes²,

Grisotto

et al. 2015

Clinica Chimica Acta

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Background 3-hydroxypalmitoleoyl-carnitine (C16:1-OH) was recently reported to be elevated in acylcarnitine profile of propionic acidemia (PA) or methylmalonic acidemia (MMA) patients during expanded newborn screening (NBS). High levels of C16:1-OH, combined with other hydroxylated long chain acylcarnitines are related to long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). Methods The acylcarnitine profile of two LCHADD patients was evaluated using liquid chromatography-tandem mass spectrometric method. A specific retention time was reported for each hydroxylated long chain acylcarnitine. The same method was applied to some neonatal dried blood spots (DBS) from PA and MMA patients presenting abnormal C16:1-OH concentrations. Results The final retention time of the peak corresponding to C16:1-OH in LCHADD patients differed from those in MMA and PA patients. Heptadecanoylcarnitine (C17) has been identified as the novel biomarker specific for PA and MMA patients through high resolution mass spectrometry (Orbitrap) experiments. We found that 21 out of 23 neonates (22 MMA, and 1PA) diagnosed through the Tuscany region NBS program had significantly higher levels of C17 compared to levels detected in controls. Twenty-three maternal deficiencies (21 vitamin B12 deficiency, 1 homocystinuria and 1 gastrin deficiency) and 82 false positive for propionylcarnitine (C3) results were also analyzed. Conclusions This paper reports on the characterization of a novel biomarker able to detect propionate disorders during expanded newborn screening (NBS). The use of this new biomarker may improve the analytical performances of NBS programs especially in laboratories where second tier tests are not performed.

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Section: Methodsmentioning

confidence: 99%

Heptadecanoylcarnitine (C17) a novel candidate biomarker for newborn screening of propionic and methylmalonic acidemias

Malvagia

Haynes²,

Grisotto

et al. 2015

Clinica Chimica Acta

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“…Multiplex MS/MS assays to screen for lysosomal storage disorders in DBS have been developed [51,52]. It was demonstrated that a single DBS specimen can be used for all the analyses.…”

Section: Metabolomic Strategies and Applications In Iemsmentioning

confidence: 99%

Integration of Proteomics and Metabolomics in Exploring Genetic and Rare Metabolic Diseases

et al. 2017

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Background: Inherited metabolic disorders or inborn errors of metabolism are caused by deficiency of enzymatic activities in the catabolism of amino acids, carbohydrates, or lipids. These disorders include aminoacidopathies, urea cycle defects, organic acidemias, defects of oxidation of fatty acids, and lysosomal storage diseases. Inborn errors of metabolism constitute a significant proportion of genetic diseases, particularly in children; however, they are individually rare. Clinical phenotypes are very variable, some of them remain asymptomatic, others manifest metabolic decompensation in neonatal age, and others encompass mental retardation at later age. The clinical manifestation of these disorders can involve different organs and/or systems. Some disorders are easily managed if promptly diagnosed and treated, whereas in other cases neither diet, vitamin therapy, nor transplantation appears to prevent multi-organ impairment. Summary: Here, we discuss the principal challenges of metabolomics and proteomics in inherited metabolic disorders. We review the recent developments in mass spectrometry-based proteomic and metabolomic strategies. Mass spectrometry has become the most widely used platform in proteomics and metabolomics because of its ability to analyze a wide range of molecules, its optimal dynamic range, and great sensitivity. The fast measurement of a broad spectrum of metabolites in various body fluids, also collected in small samples like dried blood spots, have been facilitated by the use of mass spectrometry-based techniques. These approaches have enabled the timely diagnosis of inherited metabolic disorders, thereby facilitating early therapeutic intervention. Due to its analytical features, proteomics is suited for the basic investigation of inborn errors of metabolism. Modern approaches enable detailed functional characterization of the pathogenic biochemical processes, as achieved by quantification of proteins and identification of their regulatory chemical modifications. Key Message: Mass spectrometry-based “omics” approaches most frequently used to study the molecular mechanisms underlying inherited metabolic disorders pathophysiology are described.

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“…Second, most MS-based techniques require stringency in sample preparation, and all MS-based techniques face significant challenges in terms of conversion of raw mass spectral data into interpretable readouts. Third, with a few notable exceptions in microbiology (Seng et al, 2009), drug monitoring (Vogeser and Seger, 2008) and newborn screening for inborn errors of metabolism (la Marca, 2014), MS-based techniques have seen little translation into the clinical realm, despite the fact that they have been available for decades.…”

Section: Techniques For Unbiased Screeningmentioning

confidence: 99%

Unbiased Approaches to Biomarker Discovery in Neurodegenerative Diseases

Chen‐Plotkin

2014

Neuron

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Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and frontotemporal dementia have several important features in common. They are progressive, they affect a relatively inaccessible organ, and we have no disease-modifying therapies for them. For these brain-based diseases, current diagnosis and evaluation of disease severity rely almost entirely on clinical examination, which may only be a rough approximation of disease state. Thus, the development of biomarkers – objective, relatively easily measured and precise indicators of pathogenic processes – could improve patient care and accelerate therapeutic discovery. Yet existing, rigorously tested neurodegenerative disease biomarkers are few, and even fewer biomarkers have translated into clinical use. To find new biomarkers for these diseases, an unbiased, high-throughput screening approach may be needed. In this review, I will describe the potential utility of such an approach to biomarker discovery, using Parkinson’s disease as a case example.

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Mass spectrometry in clinical chemistry: the case of newborn screening

Cited by 56 publications

References 53 publications

Heptadecanoylcarnitine (C17) a novel candidate biomarker for newborn screening of propionic and methylmalonic acidemias

Heptadecanoylcarnitine (C17) a novel candidate biomarker for newborn screening of propionic and methylmalonic acidemias

Integration of Proteomics and Metabolomics in Exploring Genetic and Rare Metabolic Diseases

Unbiased Approaches to Biomarker Discovery in Neurodegenerative Diseases

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