Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-5 (of 5 Records) |
Query Trace: De Jesús Víctor R[original query] |
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Non-derivatized Assay for the Simultaneous Detection of Amino Acids, Acylcarnitines, Succinylacetone, Creatine, and Guanidinoacetic Acid in Dried Blood Spots by Tandem Mass Spectrometry.
Asef CK , Khaksarfard KM , De Jesús VR . Int J Neonatal Screen 2016 2 (4) Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive genetic disorder which results in global developmental delay and intellectual disability. There is evidence that early treatment prevents intellectual disability and seizures. GAMT deficiency is now being discussed as a potential addition to the U.S. Recommended Uniform Screening Panel (RUSP); the availability of suitable screening methods must be considered. A neonatal screening derivatized method to quantify creatine (CRE) and guanidinoacetic acid (GAA) in dried blood spots by tandem mass spectrometry (MS/MS) has been described. Its key feature is the ability to detect CRE and GAA in the same extract generated from neonatal DBS during amino acids (AA) and acylcarnitines (AC) analysis. More laboratories are adopting non-derivatized MS/MS screening methods. We describe an improved, non-derivatized DBS extraction and MS/MS analytical method (AAAC-GAMT) which incorporates quantitation of CRE and GAA into routine analysis of amino acids, acylcarnitines, and succinylacetone. The non-derivatized AAAC-GAMT method performs comparably to the stand-alone GAMT and non-derivatized AAAC screening methods, evidencing its potential suitability for high-throughput GAMT neonatal screening. |
Factors associated with exposure to trihalomethanes, NHANES 2001-2012
Ashley David L , Smith Mitchell M , Silva Lalith K , Yoo Young M , De Jesús Víctor R , Blount Benjamin C . Environ Sci Technol 2020 54 (2) 1066-1074 Disinfection is critical for maintaining a safe water supply, but the use of chlorine or chloramine leads to exposure to disinfection byproducts (DBPs), including trihalomethanes (THMs), which have been associated with adverse reproductive outcomes and bladder cancer. The U.S. Environmental Protection Agency revised the DBP regulations starting in 1998 to further limit levels of THMs in household water. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) collected between 2001 and 2012 (with 2 years per cycle) using models with and without water-related predictors to examine the utility of including these measures. Median blood chloroform levels (25th-75th percentiles) were 16.2 (9.13-31.2) ng/L in 2001-2002 and 5.97 (2.92-12.3) ng/L in 2011-2012. Median blood bromodichloromethane (BDCM) levels (25th-75th percentiles) were 2.22 (1.06-4.61) ng/L in 2001-2002 and 1.18 (<limit of detection-2.92) ng/L in 2011-2012. THM water concentrations and measures of the recency since time spent in water use activities were associated with blood THM levels. Being in a pool/hot tub/sauna within 24 h or taking a shower/bath within 6 h of blood collection was associated with elevated blood levels of chloroform and BDCM. When possible, it is important to include recency and external dose when assessing associations to internal dose levels for nonpersistent compounds. |
Succinylacetone as primary marker to detect tyrosinemia type I in newborns and its measurement by newborn screening programs.
De Jesus VR , Adam BW , Mandel D , Cuthbert CD , Matern D . Mol Genet Metab 2014 113 67-75 Tyrosinemia type I (TYR I) is caused by autosomal recessive fumarylacetoacetate hydrolase deficiency and is characterized by development of severe liver disease in infancy and neurologic crises. If left untreated, most patients die of liver failure in the first years of life. Intervention with medication is effective when initiated during the first month of life. This improvement in the treatment of TYR I patients influenced the decision to include TYR I in the US Secretary of the Department of Health and Human Services' (HHS) Recommended Uniform Screening Panel. However, while tyrosine is routinely measured in newborn screening (NBS) by tandem mass spectrometry (MS/MS), elevated tyrosine levels are not specific to TYR I. To improve the specificity of NBS for TYR I, several assays were developed to measure succinylacetone (SUAC) in dried blood spots (DBS). SUAC is a pathognomonic marker of TYR I, and its detection by NBS MS/MS is possible. This review of the current status of NBS for TYR I in the US is the result of discussions at the HHS Secretary's (Discretionary) Advisory Committee on Heritable Disorders in Newborns and Children about the inconsistent implementation of effective NBS for TYR I in the US. We sought to understand the different TYR I screening practices in US NBS programs. Results indicate that 50 out of 51 NBS programs in the US screen for TYR I, and a successful SUAC performance evaluation scheme is available from the Centers for Disease Control and Prevention. Programmatic and methodological barriers were identified that prevent widespread adoption of SUAC measurements in NBS laboratories. However, since SUAC detection is currently the best approach to NBS for TYR I, a further delay of the addition of SUAC measurement into NBS procedures is discouraged. SUAC measurement should improve both the false positive and false negative rate in NBS for TYR I thereby yielding the desired benefits for affected patients at no expense to the overall population served. |
Improved analysis of C26:0-lysophosphatidylcholine in dried-blood spots via negative ion mode HPLC-ESI-MS/MS for X-linked adrenoleukodystrophy newborn screening.
Haynes CA , De Jesus VR . Clin Chim Acta 2012 413 1217-21 BACKGROUND: X-linked adrenoleukodystrophy (X-ALD) is the most common human peroxisomal disorder, and is caused by mutations in the peroxisomal transmembrane ALD protein (ALDP, ABCD1). The biochemical defect associated with X-ALD is an accumulation of very long-chain fatty acids (VLCFA, e.g. C24:0 and C26:0), which has been shown to result in the accumulation of C26:0-lysophosphatidylcholine (C26:0-LPC). METHODS: We describe the analysis of C26:0-LPC in dried-blood spots (DBS) using a rapid (30min) and simple extraction procedure, isocratic HPLC resolution of LPC, and structure-specific analysis via negative ion mode tandem mass spectrometry. RESULTS: In putative normal DBS specimens from newborns (N=223) C26:0-LPC was 0.09+/-0.03mcmol/l whole blood, while in peroxisomal biogenesis disorder (including X-ALD) patients (N=28) C26:0-LPC was 1.13+/-0.67mcmol/l whole blood. Both multiple reaction monitoring and a neutral loss scan (225.1Da) analysis of DBS were used to analyze LPC. CONCLUSIONS: Compared to a previous report of C26:0-LPC analysis in DBS, the method described here is simpler, faster, and more structure-specific for LPC with C26:0 acyl chains. |
Neonatal screening for lysosomal storage disorders: feasibility and incidence from a nationwide study in Austria.
Mechtler TP , Stary S , Metz TF , De Jesus VR , Greber-Platzer S , Pollak A , Herkner KR , Streubel B , Kasper DC . Lancet 2012 379 (9813) 335-41 BACKGROUND: The interest in neonatal screening for lysosomal storage disorders has increased substantially because of newly developed enzyme replacement therapies, the need for early diagnosis, and technical advances. We tested for Gaucher's disease, Pompe's disease, Fabry's disease, and Niemann-Pick disease types A and B in an anonymous prospective nationwide screening study that included genetic mutation analysis to assess the practicality and appropriateness of including these disorders in neonatal screening panels. METHODS: Specimens from dried blood spots of 34,736 newborn babies were collected consecutively from January, 2010 to July, 2010, as part of the national routine Austrian newborn screening programme. Anonymised samples were analysed for enzyme activities of acid beta-glucocerebrosidase, alpha-galactosidase, alpha-glucosidase, and acid sphingomyelinase by electrospray ionisation tandem mass spectrometry. Genetic mutation analyses were done in samples with suspected enzyme deficiency. FINDINGS: All 34,736 samples were analysed successfully by the multiplex screening assay. Low enzyme activities were detected in 38 babies. Mutation analysis confirmed lysosomal storage disorders in 15 of them. The most frequent mutations were found for Fabry's disease (1 per 3859 births), followed by Pompe's disease (1 per 8684), and Gaucher's disease (1 per 17,368). The positive predictive values were 32% (95% CI 16-52), 80% (28-99), and 50% (7-93), respectively. Mutational analysis detected predominantly missense mutations associated with a late-onset phenotype. INTERPRETATION: The combined overall proportion of infants carrying a mutation for lysosomal storage disorders was higher than expected. Neonatal screening for lysosomal storage disorders is likely to raise challenges for primary health-care providers. Furthermore, the high frequency of late-onset mutations makes lysosomal storage disorders a broad health problem beyond childhood. FUNDING: Austrian Ministry of Health, Family, and Women. |
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