2023
Validation of a targeted metabolomics panel for improved second‐tier newborn screening
Mak J, Peng G, Le A, Gandotra N, Enns G, Scharfe C, Cowan T. Validation of a targeted metabolomics panel for improved second‐tier newborn screening. Journal Of Inherited Metabolic Disease 2023, 46: 194-205. PMID: 36680545, PMCID: PMC10023470, DOI: 10.1002/jimd.12591.Peer-Reviewed Original ResearchConceptsRecommended Uniform Screening PanelMethylmalonic acidemiaNewborn screeningOrnithine transcarbamylase deficiencySecond-tier assayDisease markersGlutaric acidemia type ILong-chain acyl-CoA dehydrogenase deficiencyScreen-positive casesUniform Screening PanelLong-chain acylcarnitinesSecond-tier testingFalse-positive casesSecond-tier testBlood spot samplesAcyl-CoA dehydrogenase deficiencyMetabolomics panelMetabolic disordersTargeted metabolomics analysisPositive casesMetabolite panelNBS programsDehydrogenase deficiencyLiquid chromatography-tandem mass spectrometryScreening panel
2022
Metabolic diversity in human populations and correlation with genetic and ancestral geographic distances
Peng G, Pakstis AJ, Gandotra N, Cowan TM, Zhao H, Kidd KK, Scharfe C. Metabolic diversity in human populations and correlation with genetic and ancestral geographic distances. Molecular Genetics And Metabolism 2022, 137: 292-300. PMID: 36252453, PMCID: PMC10131177, DOI: 10.1016/j.ymgme.2022.10.002.Peer-Reviewed Original Research
2020
Ethnic variability in newborn metabolic screening markers associated with false‐positive outcomes
Peng G, Tang Y, Gandotra N, Enns GM, Cowan TM, Zhao H, Scharfe C. Ethnic variability in newborn metabolic screening markers associated with false‐positive outcomes. Journal Of Inherited Metabolic Disease 2020, 43: 934-943. PMID: 32216101, PMCID: PMC7540352, DOI: 10.1002/jimd.12236.Peer-Reviewed Original ResearchMeSH KeywordsAcyl-CoA Dehydrogenase, Long-ChainAmino Acid Metabolism, Inborn ErrorsBiomarkersBrain Diseases, MetabolicCaliforniaCongenital Bone Marrow Failure SyndromesEthnicityFalse Positive ReactionsFemaleGestational AgeGlutaryl-CoA DehydrogenaseHumansInfant, NewbornLipid Metabolism, Inborn ErrorsMaleMitochondrial DiseasesMuscular DiseasesNeonatal ScreeningOrnithine Carbamoyltransferase Deficiency DiseaseTandem Mass SpectrometryConceptsMetabolic marker levelsOrnithine transcarbamylase deficiencyMethylmalonic acidemiaClinical variablesMarker levelsBlack infantsMetabolic markersBlood metabolic markersDiverse newborn populationGlutaric acidemia type 1False-positive screensLong-chain acyl-CoA dehydrogenase deficiencyEthnicity-related differencesNewborn screening programsFalse-positive casesInborn metabolic disordersAcyl-CoA dehydrogenase deficiencySingleton babiesGestational ageBirth weightScreening programMetabolic disordersNewborn populationInfluence of ethnicityMetabolic screening
2018
Elevated methylmalonic acidemia (MMA) screening markers in Hispanic and preterm newborns
Peng G, de Fontnouvelle CA, Enns GM, Cowan TM, Zhao H, Scharfe C. Elevated methylmalonic acidemia (MMA) screening markers in Hispanic and preterm newborns. Molecular Genetics And Metabolism 2018, 126: 39-42. PMID: 30448007, PMCID: PMC6361520, DOI: 10.1016/j.ymgme.2018.11.006.Peer-Reviewed Original ResearchConceptsMarker levelsBirth weightMethylmalonic acidemiaPreterm birthHispanic infantsBlack infantsLow birth weightPreterm birth rateFalse-positive casesPreterm newbornsGestational ageFalse-positive resultsHigh prevalenceDiagnostic proceduresInfantsNon-HispanicsBirth rateNewbornsPredictive covariatesAcidemiaCombining newborn metabolic and DNA analysis for second-tier testing of methylmalonic acidemia
Peng G, Shen P, Gandotra N, Le A, Fung E, Jelliffe-Pawlowski L, Davis RW, Enns GM, Zhao H, Cowan TM, Scharfe C. Combining newborn metabolic and DNA analysis for second-tier testing of methylmalonic acidemia. Genetics In Medicine 2018, 21: 896-903. PMID: 30209273, PMCID: PMC6416784, DOI: 10.1038/s41436-018-0272-5.Peer-Reviewed Original ResearchConceptsScreen-positive newbornsMethylmalonic acidemiaMMA patientsPathogenic variantsNewborn screeningNewborn metabolic screeningLikely pathogenic variantsSecond-tier testingFalse-positive casesInborn metabolic disordersMMA casesHealthy controlsHispanic ethnicityMetabolic disordersMetabolic screeningPatientsDiverse multiethnic populationsMultiethnic populationMolecular findingsBlood spotsUnknown significanceFalse-positive outcomesNBS programsClinical performanceScreening panel
2016
Acylcarnitine Profiles Reflect Metabolic Vulnerability for Necrotizing Enterocolitis in Newborns Born Premature
Sylvester KG, Kastenberg ZJ, Moss RL, Enns GM, Cowan TM, Shaw GM, Stevenson DK, Sinclair TJ, Scharfe C, Ryckman KK, Jelliffe-Pawlowski LL. Acylcarnitine Profiles Reflect Metabolic Vulnerability for Necrotizing Enterocolitis in Newborns Born Premature. The Journal Of Pediatrics 2016, 181: 80-85.e1. PMID: 27836286, PMCID: PMC5538349, DOI: 10.1016/j.jpeds.2016.10.019.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersCaliforniaCarnitineCohort StudiesConfidence IntervalsEnterocolitis, NecrotizingFemaleFollow-Up StudiesGestational AgeHumansIncidenceInfant, NewbornInfant, PrematureIntensive Care Units, NeonatalMaleMultivariate AnalysisNeonatal ScreeningOdds RatioReproducibility of ResultsRetrospective StudiesRisk AssessmentVulnerable PopulationsConceptsModel development cohortValidation cohortAcylcarnitine levelsAcylcarnitine profilesNeonatal intensive care unitAbnormal fatty acid metabolismRetrospective cohort studyTotal parenteral nutritionDevelopment of NECIntensive care unitRisk stratification modelNewborn screening resultsDisease prevention strategiesLog unit increaseFatty acid metabolismCohort studyNecrotizing enterocolitisParenteral nutritionPreterm birthCare unitDevelopment of diseaseBirth weightBiologic surrogatesFree carnitineNewborn screeningNext-Generation Molecular Testing of Newborn Dried Blood Spots for Cystic Fibrosis
Lefterova MI, Shen P, Odegaard JI, Fung E, Chiang T, Peng G, Davis RW, Wang W, Kharrazi M, Schrijver I, Scharfe C. Next-Generation Molecular Testing of Newborn Dried Blood Spots for Cystic Fibrosis. Journal Of Molecular Diagnostics 2016, 18: 267-282. PMID: 26847993, PMCID: PMC4816703, DOI: 10.1016/j.jmoldx.2015.11.005.Peer-Reviewed Original ResearchMeSH KeywordsCosts and Cost AnalysisCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDNA Copy Number VariationsDNA PrimersDried Blood Spot TestingGenetic TestingHigh-Throughput Nucleotide SequencingHumansInfant, NewbornMultiplex Polymerase Chain ReactionNeonatal ScreeningQuality ControlReproducibility of ResultsSensitivity and SpecificityConceptsMultiplex next-generation sequencingCost-effective assayHigh-throughput screeningLengthy turnaround timeNewborn Dried Blood SpotsAmplification methodUnique designSample processingGenomic DNAMolecular assaysHigh costTurnaround timeGenetic diseasesBlood spotsCFTR analysisComplete concordanceDried Blood SpotsSingle runAssaysScreen-positive newbornsCostDetection
2009
Mitochondrial DNA analysis by multiplex denaturing high-performance liquid chromatography and selective sequencing in pediatric patients with cardiomyopathy
Schrijver I, Pique LM, Traynis I, Scharfe C, Sehnert AJ. Mitochondrial DNA analysis by multiplex denaturing high-performance liquid chromatography and selective sequencing in pediatric patients with cardiomyopathy. Genetics In Medicine 2009, 11: 118-126. PMID: 19265752, DOI: 10.1097/gim.0b013e318190356b.Peer-Reviewed Original ResearchConceptsHereditary optic neuropathyPediatric patientsWorse clinical symptomsHigh-performance liquid chromatographyDNA testingLeber's hereditary optic neuropathyIndividual sequence changesMutation analysisNovel heteroplasmic mutationClinical diagnostic useIdiopathic cardiomyopathyRare causeClinical symptomsOptic neuropathyDefinitive diagnosisPediatric cardiomyopathyAdditional functional parametersMultisystemic diseaseCardiomyopathyPathogenic changesUncertain pathogenicityLiquid chromatographyPatientsRespiratory chain activityDiagnostic use
2001
Frequency of mitochondrial transfer RNA mutations and deletions in 225 patients presenting with respiratory chain deficiencies
Jaksch M, Kleinle S, Scharfe C, Klopstock T, Pongratz D, Müller-Höcker J, Gerbitz KD, Liechti-Gallati S, Lochmuller H, Horvath R. Frequency of mitochondrial transfer RNA mutations and deletions in 225 patients presenting with respiratory chain deficiencies. Journal Of Medical Genetics 2001, 38: 665. PMID: 11584044, PMCID: PMC1734743, DOI: 10.1136/jmg.38.10.665.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultChildChild, PreschoolDNA Mutational AnalysisElectron TransportFemaleGene FrequencyGenetic VariationGenotypeHumansInfantInfant, NewbornMaleMiddle AgedMitochondria, MuscleMitochondrial DiseasesMuscle, SkeletalMutationPhenotypePolymorphism, GeneticRNARNA, MitochondrialRNA, TransferSequence DeletionConceptsMitochondrial transfer RNA (mt-tRNA) mutationsAdult patientsRespiratory chain deficiencyDistinct neurological syndromesChain deficiencyNeonatal groupPediatric groupClinical symptomsNeurological syndromeIndex patientsPathogenic mitochondrial DNA mutationsPatientsPathogenic relevanceMitochondrial DNA mutationsSkeletal musclePathogenic mutationsMuscle DNARNA mutationsMitochondrial disordersG mutationSkeletal muscle DNADeficiencyDetection rateDNA mutationsRC deficiency