International Journal of Neonatal Screening最新文献

{"title":"Universal Dried Blood Spot Screening for Congenital Cytomegalovirus: A Slovenian National Implementation Pilot.","authors":"Nika Eržen, Jernej Kovač, Barbka Repič Lampret, Urh Grošelj, Aneta Soltirovska Šalamon, Gregor Nosan","doi":"10.3390/ijns12030048","DOIUrl":"10.3390/ijns12030048","url":null,"abstract":"<p><p>Congenital cytomegalovirus infection (cCMV) is the most common congenital infection and an important cause of sensorineural hearing loss and neurodevelopmental impairment, yet many affected infants remain undetected under selective screening approaches. We conducted a prospective national pilot study to evaluate the feasibility and diagnostic yield of universal dried blood spot (DBS)-based screening for cCMV within the Slovenian newborn screening program. DBS samples collected within 72 h of life were tested by polymerase chain reaction (PCR), and screen-positive newborns underwent confirmatory urine PCR within 21 days together with standardized clinical evaluation. Among 5556 screened newborns, 13 (0.23%) screened positive and cCMV was confirmed in 10, corresponding to a lower-bound birth prevalence of 1.80 per 1000 live births (95% confidence interval, 0.98-3.31), because confirmatory testing was limited to DBS-positive newborns. None of the confirmed cases were clinically suspected at birth, and all passed newborn hearing screening. Six infants met protocol-defined criteria for symptomatic cCMV and received valganciclovir. Historical registry-based clinical case ascertainment in Slovenia corresponded to 0.09 detected cases per 1000 live births. These findings demonstrate the feasibility of universal DBS-based cCMV screening within an established newborn screening infrastructure and suggest substantial under-ascertainment under selective clinical detection pathways.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Intracerebroventricular Enzyme Replacement and Cord Blood Transplantation in Patients with Mucopolysaccharidosis Type II Diagnosed Through Newborn Screening.","authors":"Yuki Ueda, Shinsuke Hirabayashi, Masayuki Miura, Satoshi Yamada, Sachiko Nakakubo, Midori Nakajima, Takeru Goto, Jutaro Abe, Yukayo Terashita, Atsushi Manabe, Torayuki Okuyama, Kiyoshi Egawa","doi":"10.3390/ijns12030047","DOIUrl":"10.3390/ijns12030047","url":null,"abstract":"<p><p>Enzyme replacement therapy (ERT) for central nervous system symptoms and newborn screening (NBS) is available in Japan for patients with mucopolysaccharidosis type II (MPS II). Of 12 suspected cases identified through the NBS program, 3 patients were diagnosed with neuronopathic MPS II (2 directly from the screened cohort and 1 affected sibling). We reviewed the clinical courses of these patients, who were treated with intracerebroventricular (ICV) ERT using idursulfase beta (Hunterase^®) followed by umbilical cord blood transplantation (CBT). Heparan sulfate (HS) in the cerebrospinal fluid (CSF) was longitudinally measured as a therapeutic biomarker, and developmental age was evaluated. All patients achieved successful engraftment with no severe complications, except for one patient with sinusoidal obstruction syndrome. The CSF HS concentration showed a temporary increase during the ERT discontinuation period, which can be attributed to CBT, and a subsequent reduction after the resumption of ICV-ERT. The patients exhibited age-appropriate development. The pattern of change in HS indicates the importance of continuing ICV-ERT even after hematopoietic stem cell transplantation. The study results demonstrate that the combination of ICV-ERT and CBT may yield promising outcomes in patients with neuronopathic MPS II, underscoring the importance of early intervention through NBS.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethical, Legal, and Social Implications of Newborn Screening in Africa: A Scoping Review.","authors":"Victory Oghenetega Samuel, Abdullahi Adeyinka Adejare, Ushotanefe Useh","doi":"10.3390/ijns12030046","DOIUrl":"10.3390/ijns12030046","url":null,"abstract":"<p><p>Newborn screening initiatives have the potential to mitigate childhood morbidity in Africa, but they also have special ethical, legal, and social implications (ELSI) that are influenced by issues with the health system, cultural diversity, and limited resources. This scoping review explores the ELSI of newborn screening across Africa to identify key challenges, gaps, and future research needs. A systematic search identified 27 peer-reviewed studies published between 2008 and 2025, covering 12 African countries. Data were extracted on study characteristics, disease types, and ELSI dimensions from African Journals Online (AJOL), Scopus, PubMed, Web of Science, and BMJ Journals. Thematic analysis mapped recurring ethical, legal, and social concerns. Most studies examined ethical and social dimensions, while legal frameworks were rarely addressed. South Africa, Tanzania, and Ghana contributed the largest number of publications. Sickle cell disease (52%) and hearing screening (30%) were the dominant foci. Common ethical issues included informed consent, privacy, and justice; legal gaps centered on the absence of data protection and frameworks; and social concerns involved stigma, awareness, and cultural perceptions of hereditary disease. Ethical and social issues dominate NBS discourse in Africa, whereas legal oversight remains limited. To guarantee fair, reliable, and long-lasting newborn screening programs, national policy guidelines, community involvement, and context-specific ethical frameworks must be strengthened.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Clinical Pathways for Early Diagnosis and Management of SCID, SMA, and XLA Through Newborn Screening in Malaysia.","authors":"Alia Zainudin, Thin Thin Aye, Chloe Chen Sze Yun, Gaayathri Kumarasamy, Adli Ali","doi":"10.3390/ijns12030045","DOIUrl":"10.3390/ijns12030045","url":null,"abstract":"<p><p>Severe Combined Immunodeficiency (SCID), Spinal Muscular Atrophy (SMA), and X-Linked Agammaglobulinemia (XLA) are rare but life-threatening genetic disorders in infants that can lead to severe infections, progressive neuromuscular degeneration, or severe immune dysfunction associated with significant morbidity and mortality if not diagnosed early. Advances in newborn screening (NBS) technologies have enabled pre-symptomatic detection of these conditions, allowing early initiation of life-saving interventions such as hematopoietic stem cell transplantation, gene therapy, and immunoglobulin replacement therapy. However, the absence of a standardized national clinical pathway linking screening, confirmatory testing, and specialist referral in Malaysia continues to contribute to delayed diagnosis and suboptimal patient outcomes. This review examines and synthesizes current evidence on the clinical pathways for early diagnosis and management of SCID, SMA, and XLA, with particular emphasis on diagnostic workflows, screening technologies, and healthcare system challenges within the Malaysian context. The review examines disease epidemiology, consequences of delayed diagnosis, and the role of expanded NBS under the Screening for Health, Intervention, Nurturing of Every Child (SHINE) program in improving early diagnosis and management. In addition, the paper outlines the current NBS landscape, the use of multiplex real-time polymerase chain reaction (PCR) assays for simultaneous detection of T-cell receptor excision circles (TREC), kappa-deleting recombination excision circles (KREC), and survival motor neuron 1 (SMN1) gene deletion of exon 7 from dried blood spot (DBS) samples. A structured diagnostic framework incorporating screening interpretation, confirmatory testing, and urgency-based referral pathways is also proposed. By addressing current operational barriers and coordinating laboratory referral systems, expanding NBS programs could significantly improve early diagnosis and long-term outcomes for infants affected by SCID, SMA, and XLA in Malaysia.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethical and Clinical Boundaries in Genomics & Newborn Screening: A Brief Report from IPIC2025.","authors":"Raquel Yahyaoui, Lúcia Mamede, Martin Zach, James Taylor, Claire Booth, Rosalind Fisher, Věra Franková, Adli Ali, Johan Prevot, Martine Pergent, Roberta Anido de Pena, Elizabeth Rivers","doi":"10.3390/ijns12020043","DOIUrl":"10.3390/ijns12020043","url":null,"abstract":"<p><p>The Ethics Session of the International Primary Immunodeficiency Congress (IPIC), held in November 2025 and organised by the International Patient Organisation for Primary Immunodeficiencies (IPOPI), examined one of the most challenging developments emerging from genomic-enhanced newborn screening: the identification of serious, non-treatable disorders as incidental detection in programmes originally designed to detect severe combined immunodeficiency (SCID). Using a fictionalised clinical scenario based on the recent literature, the session explored the early diagnosis of ataxia-telangiectasia (AT) detected through TREC-based screening. The discussion highlighted the clinical value and psychological risks associated with presymptomatic detection, the persistent shortcomings in parental consent processes, the systemic pressures created by expanding genomic testing, and the ethical challenges surrounding the reporting and management of incidental findings in screening. The debate underscored the need for internationally coordinated frameworks to guide the management of incidental detection in newborn screening as genomic technologies become more deeply embedded in routine public health practice.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13299271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health Outcomes of Patients with Distal Urea Cycle Disorders Detected by Newborn Screening: Data from the Spanish National Registry.","authors":"Raquel Yahyaoui, Pilar Quijada-Fraile, Javier Blasco-Alonso, Inmaculada Vives, David Gil Ortega, Maria-Luz Couce, Paula Sánchez-Pintos, M Concepción García Jiménez, Silvia Meavilla Olivas, Camila García Volpe, Mariela de Los Santos Mercedes, Ángels García-Cazorla, Ana Felipe-Rucián, Lucy Dougherty-de Miguel, Ana Morais López, Ana Bergua Martínez, José David Andrade Guerrero, Sinziana Stanescu, Amaya Belanger, Mercedes Gil-Campos, María José Comino Monroy, Marcello Bellusci, Patricia Pérez-Mohand, Delia Barrio-Carreras, Belén Pérez, Elena Martín-Hernández","doi":"10.3390/ijns12020044","DOIUrl":"10.3390/ijns12020044","url":null,"abstract":"<p><p>Urea cycle disorders (UCDs) are rare inherited metabolic diseases associated with toxic hyperammonemia, leading to severe neurological damage and early mortality. Early diagnosis of distal UCDs through newborn screening (NBS) enables presymptomatic intervention; however, comparative real-world outcome data remain limited. We conducted a retrospective, multicenter study using data from the Spanish UCD Registry to describe the clinical characteristics and compare health outcomes between patients diagnosed through NBS (<i>n</i> = 40) and those diagnosed after clinical presentation (<i>n</i> = 53). Patients identified by NBS showed a markedly more favorable clinical prognosis, with a mortality rate of 2.5% compared with 15.1% in the unscreened cohort, as well as significantly lower rates of neurological involvement, fewer hospital admissions due to metabolic decompensation, and a reduced need for liver transplantation. Screening also identified a high prevalence of argininosuccinate synthetase deficiency (ASS1D) cases with attenuated biochemical profiles, highlighting the relevance of sensitive screening cutoffs. These findings provide real-world evidence that presymptomatic diagnosis through NBS is associated with improved survival and long-term neurological outcomes in patients with distal UCDs.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13300526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementation of a Prospective Birth Cohort for Newborn Screening and Early Linkage to Comprehensive Sickle Cell Disease Care in a Low-Resource Setting.","authors":"Umma A Ibrahim, Aisha B Musa, Oiza O Aliu-Isah, Hauwa A Inuwa, Zubaida L Farouk, Khadija Bulama, Aisha Mukaddas, Khadija Kamal, Rifkatu N Auta, Nafiu Hussaini, Aisha A Galadanci, Yusuf D Jobbi, Bilya S Musa, Yvonne Carroll, Lauren J Klein, Ibrahim M Idris, Michael R DeBaun, Muktar H Aliyu","doi":"10.3390/ijns12020042","DOIUrl":"10.3390/ijns12020042","url":null,"abstract":"<p><p>In sub-Saharan Africa, where approximately 75% of newborns with sickle cell disease (SCD) are born, under-five mortality remains high, partly due to the absence of newborn screening (NBS) and delayed linkage to comprehensive care. We conducted a prospective, quasi-experimental study involving two sequential newborn screening cohorts at Aminu Kano Teaching Hospital (AKTH), Kano, Nigeria (December 2022-December 2025), to evaluate the feasibility of integrating newborn screening (NBS) with early comprehensive SCD care and to identify barriers to enrollment before 3 months of age. Following an initial implementation period with suboptimal follow-up, a structured family-centered enrollment and communication strategy was introduced to improve early linkage to comprehensive care. During the pre-intervention period, 277 newborns were enrolled (33 with SCD and 244 without SCD [NSCD]), with early enrollment (≤3 months) occurring in 46.5% overall, higher among SCD than NSCD infants (72.8% vs. 43.0%). Delayed enrollment (>6 months) was more frequent among SCD infants. Following the implementation of family-centered communication strategies, 60 additional newborns were enrolled (16 SCD, 44 NSCD), and early enrollment increased to 91.7%. These findings demonstrate that low-cost, family-centered communication and tracking strategies can substantially improve early linkage to comprehensive SCD care following newborn screening in low-resource settings. Early enrollment is a critical step toward reducing morbidity and mortality among children with SCD in low-resource settings.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13300708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Dried Blood Spot Proficiency Testing Materials for Newborn Screening of Lysosomal Diseases Using Recombinant Enzymes.","authors":"Elya Courtney, Samantha L Isenberg, Timothy Lim, C Austin Pickens, Rachel Lee, Carla Cuthbert, Konstantinos Petritis","doi":"10.3390/ijns12020040","DOIUrl":"10.3390/ijns12020040","url":null,"abstract":"<p><p>Lysosomal diseases (LDs, or Lysosomal Storage Disorders) have become increasingly visible in the newborn screening community, with the addition of mucopolysaccharidosis type II (MPS-II) into the Recommended Uniform Screening Panel in August 2022 and Infantile Krabbe disease in June 2024. As more LDs are expected to be considered for screening adoption, the ability to multiplex conditions and expand proficiency testing (PT) using quality control materials is essential. This study examines the use of recombinant enzymes to produce first-tier PT materials for mucopolysaccharidosis type I, MPS-II, Gaucher, Fabry, Krabbe, Pompe, and Niemann-Pick A/B (acid sphingomyelinase deficiency)-adding four disorders to the CDC's Newborn Screening Quality Assurance Program (NSQAP) LD PT panel. Through an iterative process that included two prototype phases, two pilot phases, and external testing by up to 31 external laboratories, a new manufacturing process was developed for producing high-performing dried blood spot-based LD PT specimens. Materials were evaluated using several methods commonly employed by newborn screening laboratories, including tandem mass spectrometry with flow injection and liquid chromatography, digital microfluidics, and fluorometric assays. This novel process for producing LD PT materials offers several advantages over previous manufacturing methods that relied on immortalized cell lines from affected patients. Improved scalability, for example, has enabled NSQAP to expand LD PT enrollment internationally. Furthermore, the new process makes it easier to support future expansions of the LD screening panel. The updated specimens and expanded program were launched in January 2025.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13299422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transitioning from Laboratory-Developed Tests to a Single Commercial Reagent Kit in a National Newborn Screening Program: Impact on Analytical Performance and Harmonization.","authors":"Rachel S Carling, Zoe J Barclay, Sophie C Ward, Marie Appleton, Robert Barski, Harry Benn, Kelly Chambers, Paul Coakley, Helena Kemp, Nicola Crabbe, Sarah Dowden, Toby Greenfield, Sarah L Hogg, Saima Hussein, Rhiannon Marr, Oliver Parkes, Darren Powell, Tejswurree Ramgoolam, Joshua Ssali, Nazia Taj, Katherine Wright, Teresa H Y Wu, James R Bonham","doi":"10.3390/ijns12020041","DOIUrl":"10.3390/ijns12020041","url":null,"abstract":"<p><p>Newborn screening in England is a national program with laboratories adhering to common screening algorithms. Until recently, screening for inherited metabolic disorders was provided by ten laboratories using laboratory-developed tests (LDTs) and three using commercial assays: harmonization of results proved challenging. Introduction of hereditary tyrosinemia type 1 screening meant LDTs required modification to include the measurement of succinylacetone, and subsequent re-validation. This provided an opportunity to implement a single commercial reagent kit in all laboratories. It was anticipated that this would improve analytical performance and harmonization. This study aimed to determine whether these goals were achieved. Verification across the 13 laboratories revealed that the commercial kit reduced inter-laboratory variation for all analytes demonstrating improved harmonization. However, this was achieved by applying instrument-specific correction factors to all analytes, the magnitude of which were significant, indicating a lack of standardization. Performance of succinylacetone was limited by instrument-dependent background interference from the methionine stable isotope label, underscoring the need to establish evidence-based screening cut-off values (COV) rather than adopting published thresholds. This study emphasizes the need for traceable reference materials to improve laboratory quality and the value of screening outcome data.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13300528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Four-Year Prospective Pilot Study of Newborn Screening for Late-Onset Proximal Urea-Cycle Disorders in Hyogo Prefecture in Japan.","authors":"Tomoko Lee, Miki Matsui, Yoko Yokoyama, Ryosuke Bo, Hiroyuki Awano, Dai Kataoka, Masaaki Ueda, Toshinori Minato, Hironori Kobayashi, Yuki Hasegawa, Kei Murayama, Yasuhiro Takeshima","doi":"10.3390/ijns12020039","DOIUrl":"10.3390/ijns12020039","url":null,"abstract":"<p><p>Proximal urea-cycle disorders (PUCDs), including N-acetylglutamate synthase deficiency (NAGSD), ornithine transcarbamylase deficiency (OTCD), and carbamoyl phosphate synthase 1 deficiency (CPS1D), cause hyperammonemia and impair neurological outcomes. Early detection of late-onset forms allows presymptomatic intervention to prevent hyperammonemia; however, reliable newborn screening (NBS) markers are lacking. This prospective pilot study in Hyogo Prefecture, Japan, evaluated hypocitrullinemia as a screening marker for late-onset PUCDs. Newborns with citrulline levels below the 0.05th percentile on NBS between June 2020 and May 2024 were enrolled in the study. Confirmatory diagnosis of PUCDs was performed using plasma amino acids, urinary organic acids, and genetic testing. During the first period (101,172 newborns), 11 newborns exhibited hypocitrullinemia; 10 underwent further evaluation. One newborn was diagnosed with CPS1D (compound heterozygous <i>CPS1</i> variants); another was later diagnosed with Leigh syndrome. The remaining eight cases were false positives, often associated with prematurity, poor feeding, or gastrointestinal disorders. A second dried blood spot (DBS) card protocol was introduced in the second period (34,694 newborns), reducing false positives. One neonatal-onset OTCD case was detected, and citrulline levels were normalized in six of the seven other cases. In summary, hypocitrullinemia can identify presymptomatic PUCDs, and requesting a second DBS card reduces false positives, supporting its feasibility for incorporation into NBS programs.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13300342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}