International Journal of Neonatal Screening最新文献

{"title":"Pulse Oximetry Screening in the Newborn: Can Modifications to the Screening Algorithm Improve Detection?","authors":"Andrew K Ewer","doi":"10.3390/ijns12030053","DOIUrl":"10.3390/ijns12030053","url":null,"abstract":"<p><p>Pulse oximetry screening (POS) is a simple non-invasive tool which enables the early detection of critical congenital heart defects (CCHDs). POS has moderate sensitivity and high specificity; it is cost-effective, readily accepted by parents and healthcare professionals, and its introduction significantly reduces mortality from CCHDs. As a result, most high-income countries and many middle-income countries have introduced, or are considering introducing, POS. Despite the international uptake of POS, there is still no consensus regarding the most appropriate screening algorithm, although several have been described. In addition, this review will consider the variations-and their relative advantages and disadvantages-between POS algorithms and also explore how modifications to existing algorithms-such as the addition of a perfusion index or the incorporation of machine learning-may have the potential to improve future detection of CCHDs.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578341","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":"Reference Values of Peripheral Perfusion Index in Healthy Neonates and Preliminary Observations of Congenital Heart Disease in Tibet: A Cohort Study.","authors":"Miaomiao Wei, Yaoyao Dong, Ciren Zhuoma, Lin Peng, Youping Tian, Qing Gu, Sheng Wei, Bianba Zhuoma, Xiaojing Hu, Guoying Huang","doi":"10.3390/ijns12030054","DOIUrl":"10.3390/ijns12030054","url":null,"abstract":"<p><p>The peripheral perfusion index (PPI) is a non-invasive indicator of peripheral tissue perfusion in neonates. However, reference values for the PPI at different postnatal time points in healthy neonates residing at high altitudes, as well as early perfusion characteristics in infants with congenital heart disease (CHD) in these settings, remain inadequately defined. The primary aim was to determine the dynamic changes in and percentile-based reference values of the PPI in healthy neonates during the first 6-72 h after birth in the high-altitude region of Tibet. A secondary, exploratory aim was to observe PPI patterns in neonates with CHD born during the same period and to compare the two groups, given the limited number of CHD cases enrolled. A longitudinal cohort study was conducted among consecutively born neonates in a high-altitude region of Tibet. The PPI was measured in the right hand (pre-ductal) and either foot (post-ductal) at 6, ~12, ~24, ~48, and ~72 h after birth. Generalized Additive Models for Location, Scale and Shape (GAMLSS) were used to construct percentile reference curves for healthy neonates. Generalized Estimating Equations (GEE) were applied to evaluate differences in the PPI across time points, measurement sites, and between groups (healthy vs. CHD). A total of 1043 neonates were enrolled, including 1034 in the healthy group and only 9 CHD cases. In healthy neonates, the PPI increased progressively within the first 72 h, with a rapid rise from 6 to 24 h, a slower increase from 24 to 48 h, and stabilization between 48 and 72 h. At all time points, the lower-limb PPI was significantly higher than the upper-limb PPI (<i>p</i> < 0.001). The 50th percentile (P₅₀) values for the upper-limb PPI at 6, 12, 24, 48, and 72 h were 2.32, 2.46, 2.62, 2.63, and 2.77, respectively; corresponding values for the lower-limb PPI were 2.53, 2.64, 2.76, 2.77, and 2.90. Compared to the healthy group, neonates with CHD at high altitudes had similar PPI at 6 h. However, their PPI was significantly lower between 12 and 48 h. At 72 h, no statistically significant difference was found between the groups, likely due to the small sample size of CHD infants. Conclusions: This study provides a reference for routine perfusion assessment in stable neonates born at high altitudes. Due to the limited sample size (only 9 CHD cases), our findings on PPI changes in neonates with CHD remain preliminary. The normative PPI percentile curves established in this study offer objective baseline perfusion data for stable neonates living in high-altitude areas. Future large-scale cohort studies are still needed to validate the clinical value of the PPI as a perfusion monitoring tool in infants with CHD.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578339","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":"Hearing Screening-Driven Investigation of Newborns for Congenital Cytomegalovirus Infection at a German University Hospital.","authors":"Niko Kohmer, Lena Mistry, Thorsten Mosler, Sabine Kramer, Annette Weiß, Alfred Lennart Bissinger, Nora Doberschuetz, Ulrich Rochwalsky, Holger F Rabenau, Horst Buxmann","doi":"10.3390/ijns12030052","DOIUrl":"10.3390/ijns12030052","url":null,"abstract":"<p><p>Congenital Cytomegalovirus (cCMV) infection is the leading non-genetic cause of sensorineural hearing loss in newborns. Systematic nationwide screening programmes are lacking. Antiviral valganciclovir therapy could improve auditory outcomes if initiated within the first 30 days of life, making timely diagnosis crucial. To address this, we investigated whether a hearing screening-based protocol is suitable. Between 2015 and 2019, newborns, aged ≤21 days, with repeated abnormal newborn hearing screening (NHS) were prospectively enrolled at University Hospital Frankfurt. Oral mucosal swabs were tested for CMV DNA by real-time PCR, with confirmatory urine and blood diagnostics in positive cases. Of 2741 infants presenting for repeat NHS, 2059 (75.1%) showed normal bilateral findings. Of the 682 (24.9%) with abnormal results, 575 (84.3%) were aged >21 days and thus ineligible. A total of 107 infants (3.9%) met both criteria-abnormal NHS and aged ≤21 days-of whom 100 entered per-protocol analysis. Two (2%) were confirmed as cCMV-positive and received valganciclovir. Among the 48 infants who additionally underwent DBS testing, diagnostic sensitivity and specificity were 100%. The presented NHS-driven cCMV protocol reliably identified cCMV-infected newborns to offer timely antiviral therapy. In the absence of universal cCMV screening, this targeted approach offers a challenging but WHO screening-criteria-compliant strategy to enable timely antiviral intervention.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578636","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":"Expanding 5q-SMA Newborn Screening in Latin America: A Brazilian Model for National and Regional Implementation.","authors":"Diogo Nani, Rodrigo Holanda Mendonça, Felipe Franco da Graça, Vitoria Regia Pereira Pinheiro, Mirella Carneireiro, Bruna Glaucia Farah, Marcondes Cavalcante França, Carmen Silvia Gabetta, Graziela Polido, Cristina Iwabe, Frederico Monfardini, Alulin Tácio Quadros Santos Monteiro Fonseca, Paulo Breinis, Carmela Maggiuzzo Grindler, Carlos Eugenio Fernandez de Andrade, Athene Maria de Marco França Mauro, Edmar Zanoteli, Wilson Marques, Léa Maria Zanini Maciel, Acary Souza Bulle Oliveira, Maria da Penha Ananias Morita, Edward Yang, Vanessa Luiza Romanelli Tavares","doi":"10.3390/ijns12030050","DOIUrl":"10.3390/ijns12030050","url":null,"abstract":"<p><p>5q spinal muscular atrophy (5q-SMA) is a leading genetic cause of infant mortality. Presymptomatic intervention with disease-modifying therapies significantly improves motor outcomes, but effectiveness depends on early detection through newborn screening (NBS). Despite global 5q-SMA NBS expansion and recent Brazilian federal legislation, regional disparities and a lack of systematic monitoring hinder access to timely diagnosis and care. This study addresses these gaps by evaluating a statewide pilot program in São Paulo. We used multiplex real-time PCR to detect <i>SMN1</i> exon 7 deletions in dried blood spots, confirming <i>SMN1/2</i> copy numbers via MLPA in positive cases. Under real-world conditions, timeliness key performance indicators were evaluated to assess operational efficiency. 194,714 newborns were screened with 14 positive cases, yielding a prevalence of 1:13,908. First-tier results and treatment initiation occurred at a median of 10.8 and 28 days of life, respectively. Notably, 78.6% of patients had two <i>SMN2</i> copies, of which approximately half were symptomatic by the first evaluation, highlighting the critical need for rapid screening to prevent irreversible motor decline. Screening achieved 100% specificity. This pilot demonstrates the feasibility of 5q-SMA NBS within the Brazilian public health system, providing essential evidence to overcome logistical and socioeconomic barriers and support nationwide expansion.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578559","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 TREC/KREC Newborn Screening in a High-Birth-Rate Population: A Pilot Study of 5000 Neonates in South Kazakhstan.","authors":"Gulzada Abdushukurova, Alken Auyelova, Banu Kadyrbayeva, Ardak Ayazbekov, Dina Mussayeva, Ainash Oshibayeva, Kumissay Babayeva, Liliya Khairullina, Karlygash Sadykova, Gulnaz Nuskabaeva","doi":"10.3390/ijns12030051","DOIUrl":"10.3390/ijns12030051","url":null,"abstract":"<p><p>The early detection of Severe Combined Immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) prevents fatal outcomes. This study presents the first pilot TREC/KREC newborn screening (NBS) program in southern Kazakhstan, a high-birth-rate region, to establish local reference ranges and assess operational viability. A multiplex real-time PCR assay was used to quantify T-cell (TREC) and kappa-deleting recombination excision circles (KRECs) from dried blood spots of 5000 unselected neonates. Biomarkers were normalized to copies per 106 cells using albumin as a diploid reference gene. Regional 0.5th percentile cut-offs were established (TREC < 3165 copies/106 cells and KREC < 2554 copies/106 cells), and gender and gestational age did not significantly impact biomarker levels. While a low birth weight (≤2500 g) significantly reduced KREC levels, the extreme lower distribution tails remained unaffected, validating the use of universal, unstratified thresholds. Applying these cut-offs yielded an optimal 1.0% initial recall rate. Consistent with global incidence rates, no true positive cases were identified. The established assay and universal percentile cut-offs demonstrate high levels of analytical reliability and demographic stability. This pilot confirms the regional pediatric healthcare infrastructure's readiness for a routine, population-based NBS program without the need for complex algorithms.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578279","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":"Preliminary Data of the First Year of Newborn Screening for Metachromatic Leukodystrophy (MLD) in Lombardy.","authors":"Alessandra Vasco, Andrea Meta, Clarissa Berardo, Davide Camerlengo, Francesca Fumagalli, Davide Tonduti, Iris Fiamingo, Cristina Montrasio, Diana Postorivo, Manuela Rizzetto, Sabrina Fede, Mld-Nbs Study Group, Roberto Bozic, Francisco Ferron, Valeria Calbi, Gianvincenzo Zuccotti, Alessandro Aiuti, Giancarlo la Marca, Stephana Carelli, Cristina Cereda","doi":"10.3390/ijns12030049","DOIUrl":"10.3390/ijns12030049","url":null,"abstract":"<p><p>Metachromatic leukodystrophy (MLD) is a rare, autosomal recessive lysosomal storage disorder caused by a deficiency of the enzyme arylsulfatase A (ARSA, MIM #250100), which leads to progressive demyelination in the central and peripheral nervous systems, resulting in severe neurodegeneration and premature death. With the recent approval of the first ex vivo gene therapy for MLD, newborn screening (NBS) programs have begun to implement pilot studies for early detection, as identifying affected individuals during the pre-symptomatic therapeutic window is crucial. We present the analytical workflow and the NBS algorithm developed during the first year of MLD screening in Lombardy. The screening strategy comprised a first-tier test (1TT) using mass spectrometry to quantify sulfatide concentrations, a second-tier test (2TT) measuring ARSA enzymatic activity, and a third-tier test (3TT) based on whole-exome sequencing. A total of 16,130 newborns were screened for MLD. Of these, 6.41% required retesting (1TT), 1.53% underwent duplicate 2TT, and 0.36% proceeded to 3TT. No neonates were recalled, and no cases of MLD were identified through the screening program. The first-year implementation of MLD NBS in Lombardy demonstrates that a mass spectrometry-based sulfatide assay combined with a multi-tiered screening algorithm is feasible and reliable. Incorporating genetic analysis alongside expanded validation of additional sulfatide species may enhance specificity, reduce false positives, and facilitate timely identification of infants affected by MLD.</p>","PeriodicalId":14159,"journal":{"name":"International Journal of Neonatal Screening","volume":"12 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578250","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":"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}