N-Acetyltyrosine as a Biomarker of Parenteral Nutrition Administration in First-Tier Newborn Screening Assays.

Parenteral nutrition (PN) is a nutrient solution administered intravenously (IV) to premature babies. PN causes elevations of some amino acids in blood samples that are also biomarkers used in newborn screening (NBS). Therefore, PN status must be annotated by clinicians on dried blood spot (DBS) cards to reduce NBS laboratory burdens associated with potential false results; however, NBS laboratories continue to receive DBSs with misannotated PN status.

CDC's Laboratory Activities to Support Newborn Screening for Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) was added to the HHS Secretary's Recommended Uniform Screening Panel for newborn screening (NBS) in 2018, enabling early diagnosis and treatment of impacted infants to prevent irreversible motor neuron damage. In anticipation of supporting SMA newborn screening, scientists at the U.S.

Multiplexing Iduronate-2-Sulphatase (MPS-II) into a 7-Plex Lysosomal Storage Disorder MS/MS Assay Using Cold-Induced Phase Separation.

Mucopolysaccharidosis type II (MPS-II, Hunter syndrome, OMIM:30990) is a lysosomal storage disorder (LSD) that results in iduronate 2-sulphatase (I2S) enzyme deficiency. MPS-II was added to the Recommended Uniform Screening Panel (RUSP) in August 2022; thus, there is an increased demand for multiplexing I2S into existing LSD screening assays. After incubation with LSD synthetic substrates, extracts are cleaned using liquid-liquid extraction with ethyl acetate or protein precipitation using acetonitrile (ACN).

Harmonization of Newborn Screening Results for Pompe Disease and Mucopolysaccharidosis Type I.

In newborn screening, false-negative results can be disastrous, leading to disability and death, while false-positive results contribute to parental anxiety and unnecessary follow-ups. Cutoffs are set conservatively to prevent missed cases for Pompe and MPS I, resulting in increased falsepositive results and lower positive predictive values. Harmonization has been proposed as a way to minimize false-negative and false-positive results and correct for method differences, so we harmonized enzyme activities for Pompe and MPS I across laboratories and testing methods (Tandem Mass Spectrometry (MS/MS) or Digital Microfluidics (DMF)).

Multiplexing Homocysteine into First-Tier Newborn Screening Mass Spectrometry Assays Using Selective Thiol Derivatization.

Background: Classical homocystinuria (HCU) results from deficient cystathionine β-synthase activity, causing elevated levels of Met and homocysteine (Hcy). Newborn screening (NBS) aims to identify HCU in pre-symptomatic newborns by assessing Met concentrations in first-tier screening. However, unlike Hcy, Met testing leads to a high number of false-positive and -negative results.

Development of a Universal Second-Tier Newborn Screening LC-MS/MS Method for Amino Acids, Lysophosphatidylcholines, and Organic Acids.

First-tier MS-based newborn screening by flow injection analysis can have high presumptive positive rates, often due to isomeric/isobaric compounds or poor biomarker specificity. These presumptive positive samples can be analyzed by second-tier screening assays employing separations such as liquid chromatography-mass spectrometry (LC-MS/MS), which increases test specificity and drastically reduces false positive referrals. The ability to screen for multiple disorders in a single multiplexed test simplifies workflows and maximizes public health laboratories' resources.

Combining First and Second-Tier Newborn Screening in a Single Assay Using High-Throughput Chip-Based Capillary Electrophoresis Coupled to High-Resolution Mass Spectrometry.

Background: Most first-tier newborn screening (NBS) biomarkers are evaluated by a 2-min flow injection analysis coupled to tandem mass spectrometry (FIA-MS/MS) assay. The absence of separation prior to MS/MS analysis can lead to false positives and inconclusive results due to interferences by nominal isobars and isomers. Therefore, many presumptive positive specimens require confirmation by a higher specificity second-tier assay employing separations, which require additional time and resources prior to patient follow-up.

Harmonizing Newborn Screening Laboratory Proficiency Test Results Using the CDC NSQAP Reference Materials.

Newborn screening (NBS) laboratories cannot accurately compare mass spectrometry-derived results and cutoff values due to differences in testing methodologies. The objective of this study was to assess harmonization of laboratory proficiency test (PT) results using quality control (QC) data. Newborn Screening Quality Assurance Program (NSQAP) QC and PT data reported from 302 laboratories in 2019 were used to compare results among laboratories.

Infants with Congenital Disorders Identified Through Newborn Screening - United States, 2015-2017.

Newborn screening (NBS) identifies infants at risk for congenital disorders for which early intervention has been shown to improve outcomes (1). State public health programs are encouraged to screen for disorders on the national Recommended Uniform Screening Panel (RUSP), which increased from 29 disorders in 2005 to 35 in 2018.* The RUSP includes hearing loss (HL) and critical congenital heart defects, which can be detected through point-of-care screening, and 33 disorders detected through laboratory screening of dried blood spot (DBS) specimens.

Assessing the Performance of Dried-Blood-Spot DNA Extraction Methods in Next Generation Sequencing.

An increasing number of newborn screening laboratories in the United States and abroad are moving towards incorporating next-generation sequencing technology, or NGS, into routine screening, particularly for cystic fibrosis. As more programs utilize this technology for both cystic fibrosis and beyond, it is critical to identify appropriate DNA extraction methods that can be used with dried blood spots that will result in consistent, high-quality sequencing results. To provide comprehensive quality assurance and technical assistance to newborn screening laboratories wishing to incorporate NGS assays, CDC's Newborn Screening and Molecular Biology Branch designed a study to evaluate the performance of nine commercial or laboratory-developed DNA extraction methods that range from a highly purified column extraction to a crude detergent-based no-wash boil prep.

The Newborn Screening Quality Assurance Program at the Centers for Disease Control and Prevention: Thirty-five Year Experience Assuring Newborn Screening Laboratory Quality.

Newborn screening is the largest genetic testing effort in the United States and is considered one of the ten great public health achievements during the first 10 years of the 21 century. For over 35 years, the Newborn Screening Quality Assurance Program (NSQAP) at the US Centers for Disease Control and Prevention has helped NBS laboratories ensure that their testing does not delay diagnosis, minimizes false-positive reports, and sustains high-quality testing performance. It is a multi-component program that provides comprehensive quality assurance services for dried blood spot testing.

Succinylacetone as primary marker to detect tyrosinemia type I in newborns and its measurement by newborn screening programs.

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.

Expanded newborn screening in Puerto Rico and the US Virgin Islands: education and barriers assessment.

Purpose: The implementation of the expanded newborn screening panel of 29 disorders recommended by the American College of Medical Genetics in Puerto Rico and United States Virgin Islands is still in development or in early stages. Efforts in the territories are complicated by educational and resource barriers that generate a wide gap between the islands and the US mainland.

Methods: To meet immediate educational needs, we conducted in-services for local newborn screening professionals.

Diagnosis of inherited disorders of galactose metabolism.

Galactose metabolism occurs through an evolutionarily conserved pathway in which galactose and uridine diphosphoglucose are converted to glucose-1-phosphate and uridine diphosphogalactose through the action of three sequential enzymes: galactokinase (GALK, EC 2.7.1.

Marital status and variability in cortisol excretion in postmenopausal women.

Based on the premise that acute and chronic stresses stimulate and suppress cortisol secretion, respectively, and the hypothesis that marriage provides a buffer to stress, we tested whether extreme values of serum cortisol concentrations would be less likely in married women than in unmarried women. Three hundred women were recruited from two central Connecticut communities. Cortisol was measured in overnight urine samples using liquid chromatography-tandem mass spectrometry.

Leadership and management training for residents and fellows: a curriculum for future medical directors.

Context: Management of laboratories and pathology practices is increasingly complex. Residents and fellows in laboratory medicine and pathology need more structured curricula in leadership and management (L&M) training to function as medical and laboratory directors.

Objective: To define a curriculum that provides basic competency in L&M for residents and fellows in pathology.

Cell type-specific regulation of von Willebrand factor expression by the E4BP4 transcriptional repressor.

Mechanisms of tissue-restricted patterns of von Willebrand factor (VWF) expression involve activators and repressors that limit expression to endothelial cells and megakaryocytes. The relative transcriptional activity of the proximal VWF promoter was assessed in VWF-producing and -nonproducing cells, and promoter activity was highest in endothelial cells followed by megakaryocytes. Only basal VWF promoter activity was seen in nonendothelial cells.

Quantitative assay of plasma homocysteine thiolactone by gas chromatography/mass spectrometry.

Enzymatic cyclization of homocysteine forms a reactive thiolactone that may play an important role in its cardiovascular toxicity, but reliable quantitation of the free thiolactone metabolite in physiological fluids has not been reported. We have therefore used a highly selective gas chromatography/mass spectrometry (GC/MS) technique combined with the sensitivity of negative chemical ionization (NCI) to develop a quantitative method for the detection of homocysteine thiolactone (HcyTL) in plasma. To improve accuracy the deuterated isomer d(4)-HcyTL was synthesized and added to plasma as internal standard.