International Journal of Neonatal Screening

22 pages, 2326 KiB

Open AccessArticle

Evaluation of Neonatal Screening Programs for Tyrosinemia Type 1 Worldwide

by Allysa M. Kuypers, Marelle J. Bouva, J. Gerard Loeber, Anita Boelen, Eugenie Dekkers, Konstantinos Petritis, C. Austin Pickens, The ISNS Representatives, Francjan J. van Spronsen and M. Rebecca Heiner-Fokkema

Int. J. Neonatal Screen. 2024, 10(4), 82; https://doi.org/10.3390/ijns10040082 - 16 Dec 2024

Abstract

In The Netherlands, newborn screening (NBS) for tyrosinemia type 1 (TT1) uses dried blood spot (DBS) succinylacetone (SUAC) as a biomarker. However, high false-positive (FP) rates and a false-negative (FN) case show that the Dutch TT1 NBS protocol is suboptimal. In search of [...] Read more.

In The Netherlands, newborn screening (NBS) for tyrosinemia type 1 (TT1) uses dried blood spot (DBS) succinylacetone (SUAC) as a biomarker. However, high false-positive (FP) rates and a false-negative (FN) case show that the Dutch TT1 NBS protocol is suboptimal. In search of optimization options, we evaluated the protocols used by other NBS programs and their performance. We distributed an online survey to NBS program representatives worldwide (N = 41). Questions focused on the organization and performance of the programs and on changes since implementation. Thirty-three representatives completed the survey. TT1 incidence ranged from 1/13,636 to 1/750,000. Most NBS samples are taken between 36 and 72 h after birth. Most used biomarkers were DBS SUAC (78.9%), DBS Tyrosine (Tyr; 5.3%), or DBS Tyr with second tier SUAC (15.8%). The pooled median cut-off for SUAC was 1.50 µmol/L (range 0.3–7.0 µmol/L). The median cut-off from programs using laboratory-developed tests was significantly higher (2.63 µmol/L) than the medians from programs using commercial kits (range 1.0–1.7 µmol/L). The pooled median cut-off for Tyr was 216 µmol/L (range 120–600 µmol/L). Overall positive predictive values were 27.3% for SUAC, 1.2% for Tyr solely, and 90.1% for Tyr + SUAC. One FN result was reported for TT1 NBS using SUAC, while three FN results were reported for TT1 NBS using Tyr. The NBS programs for TT1 vary worldwide in terms of analytical methods, biochemical markers, and cut-off values. There is room for improvement through method standardization, cut-off adaptation, and integration of new biomarkers. Further enhancement is likely to be achieved by the application of post-analytical tools. Full article

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16 pages, 4066 KiB

Open AccessArticle

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

by C. Austin Pickens, Samyukta Sah, Rahul Chandrappa, Samantha L. Isenberg, Elya R. Courtney, Timothy Lim, Donald H. Chace, Rachel Lee, Carla Cuthbert and Konstantinos Petritis

Int. J. Neonatal Screen. 2024, 10(4), 81; https://doi.org/10.3390/ijns10040081 - 10 Dec 2024

Abstract

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 [...] Read more.

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. N-acetyltyrosine (NAT), a water-soluble tyrosine analog used to increase tyrosine bioavailability in PN solutions, can be used as a blood-based biomarker of PN administration in NBS assays. Residual DBS specimens and manufactured DBSs were used in analyses. The assay was developed and validated using flow injection analysis tandem mass spectrometry (FIA-MS/MS) for the detection of NAT. NAT was only present in neonate DBSs with annotated PN administration and was multiplexed into first-tier newborn screening assays. NAT was highly correlated with amino acids present in PN solutions, such as arginine, leucine, methionine, phenylalanine, and valine. In our sample cohort, we determined an NAT cutoff could aid the identification of misannotated neonates administered PN. We also report the Amadori rearrangement product valine–hexose (Val-Hex) was quantifiable in neonates administered PN, which we suspect forms in the PN solution and/or IV lines. Here, we present the first known use of NAT as a biomarker of PN administration, which is currently being piloted by two U.S. NBS laboratories. NAT and Val-Hex can aid the identification of misannotated DBSs from neonates administered PN, thus decreasing false positive rates. Full article

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11 pages, 412 KiB

Open AccessArticle

Newborn Screening for Six Primary Conditions in a Clinical Setting in Morocco

by Sara El Janahi, Mounir Filali, Zakia Boudar, Amina Akhattab, Rachid El Jaoudi, Najib Al Idrissi, Nouzha Dini, Chakib Nejjari, Raquel Yahyaoui, Michele A. Lloyd-Puryear and Hassan Ghazal

Int. J. Neonatal Screen. 2024, 10(4), 80; https://doi.org/10.3390/ijns10040080 - 4 Dec 2024

Abstract

Newborn screening (NBS) represents an important public health measure for the early detection of specified disorders; such screening can prevent disability and death, not only from metabolic disorders but also from endocrine, hematologic, immune, and cardiac disorders. Screening for critical congenital conditions affecting [...] Read more.

Newborn screening (NBS) represents an important public health measure for the early detection of specified disorders; such screening can prevent disability and death, not only from metabolic disorders but also from endocrine, hematologic, immune, and cardiac disorders. Screening for critical congenital conditions affecting newborns’ health is a great challenge, especially in developing countries such as Morocco, where NBS program infrastructure is lacking. In addition, the consanguinity rate is high in Morocco. This study aimed to demonstrate the feasibility of integrating NBS into a diagnostic laboratory for routine analysis. Six primary severe conditions were included: congenital hypothyroidism (CH), cystic fibrosis (CF), phenylketonuria (PKU), glucose-6-phosphate dehydrogenase deficiency (G6PD), congenital adrenal hyperplasia (CAH), and hemoglobinopathies. Methods: A retrospective investigation was carried out to examine the outcomes of NBS in Casablanca, Morocco. A total of 5511 newborn blood samples were collected via heel-prick sampling and tested for the above disorders. Most of the samples were collected within the third and sixth days of birth. The dried blood spots were analyzed via a quantitative immunofluorescence technique and isoelectric focusing. Results: A total of 72 newborns had one of the six pathological conditions. The most prevalent disorders were hemoglobinopathies, which were identified in 47 newborns (0.9%), with 29 having HbC carrier status (0.5%), 15 having Hb S carrier status (0.3%), and 3 having an Hb Bart’s carrier profile (0.05%). This was followed by G6PD deficiency, which was found to affect 16 newborns (0.32% of cases). CF was found in one case (0.02%), whereas five newborns (0.09%) tested positive for CAH. Additionally, two newborns (0.04%) tested positive for CH, and one newborn tested positive for PKU (0.02%). Conclusion: Our findings underscore the importance and success of NBS programs in preventing morbidity and mortality and improving the quality of life of affected neonates. The significant gap in data and research on these disorders within the Moroccan population highlights the urgent need to integrate NBS into routine practice in diagnostic laboratories across Morocco. This integration is crucial for enhancing the health and well-being of Moroccan newborns. Full article

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10 pages, 479 KiB

Open AccessArticle

Newborn Screening for Acid Sphingomyelinase Deficiency: Prevalence and Genotypic Findings in Italy

by Vincenza Gragnaniello, Chiara Cazzorla, Daniela Gueraldi, Christian Loro, Elena Porcù, Leonardo Salviati, Alessandro P. Burlina and Alberto B. Burlina

Int. J. Neonatal Screen. 2024, 10(4), 79; https://doi.org/10.3390/ijns10040079 - 4 Dec 2024

Abstract

Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder with a broad clinical spectrum. Early diagnosis and initiation of treatment are crucial for improving outcomes, yet the disease often goes undiagnosed due to its rarity and phenotypic heterogeneity. This study aims to [...] Read more.

Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder with a broad clinical spectrum. Early diagnosis and initiation of treatment are crucial for improving outcomes, yet the disease often goes undiagnosed due to its rarity and phenotypic heterogeneity. This study aims to evaluate the feasibility and disease incidence of newborn screening (NBS) for ASMD in Italy. Dried blood spot samples from 275,011 newborns were collected between 2015 and 2024 at the Regional Center for Expanded NBS in Padua. Acid sphingomyelinase activity was assayed using tandem mass spectrometry. Deidentified samples with reduced enzyme activity underwent second-tier testing with LysoSM quantification and SMPD1 gene analysis. Two samples were identified with reduced sphingomyelinase activity and elevated LysoSM levels. Both carried two SMPD1 variants, suggesting a diagnosis of ASMD. Molecular findings included novel and previously reported variants, some of uncertain significance. The overall incidence was 1 in 137,506 newborns and the PPV was 100%. This study demonstrates the feasibility of NBS for ASMD in Italy and provides evidence of a higher disease incidence than clinically reported, suggesting ASMD is an underdiagnosed condition. Optimized screening algorithms and second-tier biomarker testing can enhance the accuracy of NBS for ASMD. The long-term follow-up of identified cases is necessary for genotype–phenotype correlation and improving patient management. Full article

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13 pages, 1644 KiB

Open AccessArticle

Newborn Genetic Screening Improves the Screening Efficiency for Congenital Hypothyroidism: A Prospective Multicenter Study in China

by Liang Ye, Yinhong Zhang, Jizhen Feng, Cidan Huang, Xiaohua Wang, Lianshu Han, Yonglan Huang, Hui Zou, Baosheng Zhu and Jingkun Miao

Int. J. Neonatal Screen. 2024, 10(4), 78; https://doi.org/10.3390/ijns10040078 - 29 Nov 2024

Abstract

Newborn congenital hypothyroidism (CH) screening has been widely used worldwide. The objective of this study was to evaluate the effectiveness of applying biochemical and gene panel sequencing as screening tests for CH and to analyze the mutation spectrum of CH in China. Newborns [...] Read more.

Newborn congenital hypothyroidism (CH) screening has been widely used worldwide. The objective of this study was to evaluate the effectiveness of applying biochemical and gene panel sequencing as screening tests for CH and to analyze the mutation spectrum of CH in China. Newborns were prospectively recruited from eight hospitals in China between February and December 2021. Clinical characteristics were collected. Second-generation sequencing was used to detect four CH-related genes, and the genetic patterns of the pathogenic genes were analyzed. We analyzed the relationship between genotype and biochemical phenotype. A total of 29,601 newborns were screened for CH. Gene panel sequencing identified 18 patients, including 10 patients affected by biochemically and genetically screened disorders and 8 patients affected by solely genetically screened disorders. The predictive positive value of genetic screening was 34.62%, which was much greater than that of biochemical screening alone (17.99%). A total of 94 cases of congenital thyroid dysfunction were confirmed by biochemical and genetic screening, including 30 CHs and 64 isolated hyperthyrotropinemia (HTT), with an incidence of 1/987 for CH and 1/463 for HTT, and a total incidence of 1/315 for hypothyroidism. The incidence rate and number of patients in Jinan were the highest, and the incidence rates in Shijiazhuang and Shanghai were the lowest. The gene mutation rate in this study was 19.1%, mainly DUOX2 mutation. The most common variant of DUOX2 was c.1588A>T(p.Lys530*). There was only a difference in sFT4 between groups with gene mutations and those without mutations. Genetic screening is a supplement to biochemical screening. Combining biochemical screening with genetic screening is useful for improving screening efficiency. The incidence of CH in China according to a multicenter study of nearly 30,000 NBS surveys was 1/315. DUOX2 gene mutations are commonly detected in these patients. Full article

(This article belongs to the Special Issue Newborn Screening for Congenital Hypothyroidism)

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8 pages, 265 KiB

Open AccessArticle

Evaluation of a New Tandem Mass Spectrometry Method for Sickle Cell Disease Newborn Screening

by Céline Renoux, Estelle Roland, Séverine Ruet, Sarah Zouaghi, Marie Michel, Philippe Joly, Cécile Feray, Fanny Zhao, Déborah Gavanier, Pascal Gaucherand, Fanny Roumieu, Giovanna Cannas, Salima Merazga, Philippe Connes, Gilles Renom, Jérôme Massardier and David Cheillan

Int. J. Neonatal Screen. 2024, 10(4), 77; https://doi.org/10.3390/ijns10040077 - 26 Nov 2024

Abstract

In France, sickle cell disease newborn screening (SCD NBS) has been targeted to at-risk regions since 1984, but generalization to the whole population will be implemented from November 2024. Although tandem mass spectrometry (MS/MS) is already used for the NBS of several inherited [...] Read more.

In France, sickle cell disease newborn screening (SCD NBS) has been targeted to at-risk regions since 1984, but generalization to the whole population will be implemented from November 2024. Although tandem mass spectrometry (MS/MS) is already used for the NBS of several inherited metabolic diseases, its application for SCD NBS has not been widely adopted worldwide. The aim of this study was to evaluate a dedicated MS/MS kit (Targeted MS/MS Hemo, ZenTech, LaCAR Company, Liege, Belgium) for SCD NBS and to compare the results obtained with those from an NBS reference center using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) and cation-exchange high-performance liquid chromatography (CE-HPLC, Variant NBS, Biorad Laboratories, Inc., Hercules, CA, USA) as confirmatory method. The MS/MS Hemo kit was used according to the manufacturer’s instructions and performed on a Waters Xevo TQ-D (Waters Corporation, USA). The software provided by the manufacturer was used for the calculation and analysis of peptide signal ratios. Among the 1333 samples, the results of 1324 samples were consistent with the HPLC and/or MALDI-TOF results (1263 FA, 50 FAS, 7 FAC, 1 FAO-Arab, and 3 FS). All the discordant results (one FAS on MS/MS vs. FA in CE-HPLC, one FA on MS/MS vs. FAS in CE-HPLC, seven FS on MS/MS vs. FAS in CE-HPLC) were corrected after modifying the peptide signal ratios thresholds, allowing the MS/MS Hemo kit to achieve near-100% sensitivity and specificity for SCD NBS. In conclusion, the MS/MS Hemo kit appears to be an effective method for SCD NBS, particularly for laboratories already equipped with MS/MS technology. However, these results should be confirmed in a larger cohort including a greater number of positive samples for SCD. Full article

10 pages, 1690 KiB

Open AccessArticle

Cystic Fibrosis Screening Efficacy and Seasonal Variation in California: 15-Year Comparison of IRT Cutoffs Versus Daily Percentile for First-Tier Testing

by Stanley Sciortino, Steve Graham, Tracey Bishop, Jamie Matteson, Sarah Carter, Cindy H. Wu and Rajesh Sharma

Int. J. Neonatal Screen. 2024, 10(4), 76; https://doi.org/10.3390/ijns10040076 - 22 Nov 2024

Abstract

The California Genetic Disease Screening Program (GDSP) employs a fixed immunoreactive trypsinogen (IRT) cutoff followed by molecular testing to screen newborns for cystic fibrosis (CF). The cutoffs approximate a 1.6% yearly IRT screen-positive rate; however, seasonal variation in IRT population means has led [...] Read more.

The California Genetic Disease Screening Program (GDSP) employs a fixed immunoreactive trypsinogen (IRT) cutoff followed by molecular testing to screen newborns for cystic fibrosis (CF). The cutoffs approximate a 1.6% yearly IRT screen-positive rate; however, seasonal variation in IRT population means has led us to develop a model to establish fixed IRT cutoffs that anticipate seasonal variation and minimize missed cases below cutoff. We utilized an ARIMA model to fit monthly IRT screen-positive percentiles and estimated regular seasonal expectations. We established a retrospective cohort followed for at least 1.5 years to capture missed false-negative CF cases. We compared missed CF cases identified by seasonal cutoffs vs. floating cutoffs. GDSP screened 7,410,003 newborns, from July 2007 to December 2022, and missed 36 CF cases below the fixed cutoff; five of the 36 were within 3 ng/mL below the cutoff. There was a regular, seasonal cycle that varied from 1.4% in summer to 1.8% in winter. We would have missed 59 CF cases using a 1.6% daily floating cutoff. California would need to use a 4% daily floating cutoff to improve our current detection rate, which would double the number of specimens sent for costly molecular analysis. Full article

(This article belongs to the Special Issue Advances in Cystic Fibrosis Newborn Screening: From Laboratory Testing to Diagnosis)

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3 pages, 144 KiB

Open AccessCommentary

American College of Medical Genetics and Genomics ACT Sheets Are a Vital Resource for State Newborn Screening Programs

by Virginia Sack, Sara Etienne, Grace Beal, Sarah Bradley and Michele Caggana

Int. J. Neonatal Screen. 2024, 10(4), 75; https://doi.org/10.3390/ijns10040075 - 19 Nov 2024

Abstract

The American College of Medical Genetics and Genomics (ACMG) and the National Coordinating Center for the Regional Genetics Networks (NCC)-developed ACT sheets are a vital resource for state newborn screening (NBS) programs. They allow NBS programs to be able to provide up-to-date, just-in-time [...] Read more.

The American College of Medical Genetics and Genomics (ACMG) and the National Coordinating Center for the Regional Genetics Networks (NCC)-developed ACT sheets are a vital resource for state newborn screening (NBS) programs. They allow NBS programs to be able to provide up-to-date, just-in-time disorder information to primary care providers (PCPs). Their continued availability is necessary to ensure that all babies identified by newborn screening receive appropriate evaluation and care. Full article

8 pages, 237 KiB

Open AccessCase Report

DNAJC12 Deficiency, an Emerging Condition Picked Up by Newborn Screening: A Case Illustration and a Novel Variant Identified

by Tsz Sum Wong, Sheila Suet Na Wong, Anne Mei Kwun Kwok, Helen Wu, Hiu Fung Law, Shirley Lam, Matthew Chun Wing Yeung, Toby Chun Hei Chan, Gordon Leung, Chloe Miu Mak, Kiran Moti Belaramani and Cheuk Wing Fung

Int. J. Neonatal Screen. 2024, 10(4), 74; https://doi.org/10.3390/ijns10040074 - 19 Nov 2024

Abstract

DNAJC12 deficiency is a recently described inherited metabolic disorder resulting in hyperphenylalaninemia and neurotransmitter deficiency. The effect of treatment on the prevention of neurological manifestations in this newly reported and heterogenous disorder is not fully understood, and the optimal treatment strategy remains to [...] Read more.

DNAJC12 deficiency is a recently described inherited metabolic disorder resulting in hyperphenylalaninemia and neurotransmitter deficiency. The effect of treatment on the prevention of neurological manifestations in this newly reported and heterogenous disorder is not fully understood, and the optimal treatment strategy remains to be elucidated. The global or regional incidence of the disease is yet to be estimated. Here, we report the first individual diagnosed with DNAJC12 deficiency in Hong Kong; the condition was picked up by newborn screening due to hyperphenylalaninemia after ruling out phenylalanine hydroxylase deficiency and other tetrahydrobiopterin related disorders. Compound heterozygous variants in the DNAJC12 gene were identified, which included a novel missense change and a nonsense pathogenic variant. Treatment with neurotransmitter precursors (tetrahydrobiopterin, levodopa, and oxitriptan) was initiated at four months of age, and dietary protein restriction was started at four years and six months of age. He remains asymptomatic at four and a half years of age, apart from having mildly impaired socio-communication and language development. In this report, we discuss the current diagnostic approach to hyperphenylalaninemia in newborn screening and the uncertainties that exist in the clinical outcome from earlier detection, treatment, and monitoring of DNAJC12-deficiency patients. Full article

15 pages, 243 KiB

Open AccessArticle

Psychological Impact of Presymptomatic X-Linked ALD Diagnosis and Surveillance: A Small Qualitative Study of Patient and Parent Experiences

by Cecilie S. Videbæk, Sabine W. Grønborg, Allan M. Lund and Mette L. Olesen

Int. J. Neonatal Screen. 2024, 10(4), 73; https://doi.org/10.3390/ijns10040073 - 24 Oct 2024

Abstract

X-linked adrenoleukodystrophy (ALD) is a rare metabolic disorder. Symptoms range from cerebral demyelination (cALD) to adrenal insufficiency and slowly progressive myeloneuropathy. cALD is fatal if not treated with hematopoietic cell transplantation in the early stages of the disease course. This can be achieved [...] Read more.

X-linked adrenoleukodystrophy (ALD) is a rare metabolic disorder. Symptoms range from cerebral demyelination (cALD) to adrenal insufficiency and slowly progressive myeloneuropathy. cALD is fatal if not treated with hematopoietic cell transplantation in the early stages of the disease course. This can be achieved through cascade testing or newborn screening (NBS). Due to the lack of predictive measures of disease trajectory, patients are monitored with frequent MRI scans and hormone testing to ensure timely intervention. With this study, we wanted to explore how the diagnosis of ALD, before the development of cALD, and the follow-up program affected patients and their parents. Using semi-structured interviews, we interviewed seven parents of children with ALD aged 3–11 and four patients with ALD aged 18–25. Because NBS for ALD has not been implemented in Denmark, the patients were identified through either cascade testing or after having presented with adrenal insufficiency. We generated five themes: (I) ALD patients maintained mental resilience despite diagnosis and surveillance; (II) patients’ concerns matured with age and centered around situations that confronted them with their patient status; (III) parents of children with ALD had both short-term and long-term worries for their children’s health; (IV) parents took on a huge psychological burden; and (V) due to its rarity, the diagnosis of ALD evoked a sense of isolation and disease-related loneliness. Overall, we found a large discrepancy in the experiences reported by parents and patients. Despite the small sample size, we identified patterns that suggest that while the early diagnosis took a significant psychological toll on the parents, patients lived relatively carefree lives despite their ALD diagnosis. Full article

(This article belongs to the Special Issue Psychosocial Impact of Positive Newborn Screening)

10 pages, 1370 KiB

Open AccessArticle

Incidence of Inborn Errors of Metabolism and Endocrine Disorders Among 40965 Newborn Infants at Riyadh Second Health Cluster of the Ministry of Health Saudi Arabia

by Abdullah S. Alshehri, Abdul A. Peer-Zada, Abeer A. Algadhi, Abdulwahed Aldehaimi, Mohammed A. Saleh, Aziza M. Mushiba, Eissa A. Faqeih and Ali M. AlAsmari

Int. J. Neonatal Screen. 2024, 10(4), 72; https://doi.org/10.3390/ijns10040072 - 16 Oct 2024

Abstract

Inborn errors of metabolism (IEM) and endocrine disorders are common genetic conditions in the Saudi population with the incidence rate often underestimated. Newborn screening (NBS) using various disease panels provides the first line in the early detection and intervention among infants with a [...] Read more.

Inborn errors of metabolism (IEM) and endocrine disorders are common genetic conditions in the Saudi population with the incidence rate often underestimated. Newborn screening (NBS) using various disease panels provides the first line in the early detection and intervention among infants with a high risk of IEM. Here we aim to assess the incidence of screening disorders and provide an overview of the NBS program at the Ministry of Health Tertiary Care King Fahad Medical City. Dried blood spots (DBS) from 40,965 newborn infants collected on the second day after birth were analyzed for 20 disorders. The total number of positive screen (“repeat”) samples over 10 years was about 1% (n = 382/40,965). The true positive result rate was 15.3% (n = 46/301) with the recall rates of individual disorders ranging from 0.26% (95% CI, 0.17–0.69) to 2.6% (95% CI, 2.19–3.05). The false positive result rate was 84.7% (n = 255/301) with biotinidase activity found to be the most common cause of the second sample repeat. The overall incidence of the screened diseases was 1:891 (95% CI, 11.61–12.47). CH and CAH are the most prevalent among endocrine disorders with an incidence of 1:4097 (95% CI, 2.19–3.05), and PA and ASA among the IEM with an incidence of 1:10,241 (95% CI, 0.09–0.95). In summary, we provide updated data and our experience on the incidence of various IEM and endocrine disorders among the Saudi population, highlight the role of false positive results of biotinidase activity that can increase the recall rate and lead to overestimation of the incidence data, and recommend multicenter studies to achieve a successful national NBS program. Full article

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22 pages, 372 KiB

Open AccessSystematic Review

A Systematic Literature Review on the Global Status of Newborn Screening for Mucopolysaccharidosis II

by Olulade Ayodele, Daniel Fertek, Obaro Evuarherhe, Csaba Siffel, Jennifer Audi, Karen S. Yee and Barbara K. Burton

Int. J. Neonatal Screen. 2024, 10(4), 71; https://doi.org/10.3390/ijns10040071 - 10 Oct 2024

Abstract

A systematic literature review was conducted to determine the global status of newborn screening (NBS) for mucopolysaccharidosis (MPS) II (Hunter syndrome; OMIM 309900). Electronic databases were searched in July 2023 for articles referencing NBS for lysosomal storage diseases: 53 featured MPS II. Until [...] Read more.

A systematic literature review was conducted to determine the global status of newborn screening (NBS) for mucopolysaccharidosis (MPS) II (Hunter syndrome; OMIM 309900). Electronic databases were searched in July 2023 for articles referencing NBS for lysosomal storage diseases: 53 featured MPS II. Until recently, only Taiwan and two US states (Illinois and Missouri) formally screened newborns for MPS II, although pilot programs have been conducted elsewhere (Japan, New York, and Washington). In 2022, MPS II was added to the US Recommended Uniform Screening Panel, with increased uptake of NBS anticipated across the USA. While the overall MPS II birth prevalence, determined from NBS initiatives, was higher than in previous reports, it was lower in the USA (approximately 1 in 73,000 according to recent studies in Illinois and Missouri) than in Asia (approximately 1 in 15,000 in Japan). NBS programs typically rely on tandem mass spectrometry quantification of iduronate-2-sulfatase activity for first-tier testing. Diagnosis is often confirmed via molecular genetic testing and/or biochemical testing but may be complicated by factors such as pseudodeficiency alleles and variants of unknown significance. Evidence relating to MPS II NBS is lacking outside Taiwan and the USA. Although broad benefits of NBS are recognized, few studies specifically explored the perspectives of families of children with MPS II. Full article

10 pages, 1264 KiB

Open AccessArticle

The Value of Reducing Inconclusive and False-Positive Newborn Screening Results for Congenital Hypothyroidism, Congenital Adrenal Hyperplasia and Maple Syrup Urine Disease in The Netherlands

by Rosalie C. Martens, Anita Boelen, Michèle H. van der Kemp, Annet M. Bosch, Eveline M. Berghout, Gert Weijman, Nitash Zwaveling-Soonawala, Rendelien K. Verschoof-Puite, Robert de Jonge, Sabine E. Hannema, Judith E. Bosmans and Annemieke C. Heijboer

Int. J. Neonatal Screen. 2024, 10(4), 70; https://doi.org/10.3390/ijns10040070 - 8 Oct 2024

Abstract

Inconclusive and false-positive newborn screening (NBS) results can cause parental stress and increase healthcare expenditures. These results can be reduced by improving NBS algorithms. This was recently done for Congenital Hypothyroidism (CH), Congenital Adrenal Hyperplasia (CAH) and Maple Syrup Urine Disease (MSUD) in [...] Read more.

Inconclusive and false-positive newborn screening (NBS) results can cause parental stress and increase healthcare expenditures. These results can be reduced by improving NBS algorithms. This was recently done for Congenital Hypothyroidism (CH), Congenital Adrenal Hyperplasia (CAH) and Maple Syrup Urine Disease (MSUD) in the Dutch NBS program. The current study estimates the financial consequences of these improved algorithms related to the reduction in inconclusive results and false-positives. For each improved algorithm, the care pathway of an inconclusive/false-positive result was analyzed. The costs associated with the improvements, based on the change in inconclusive results/false-positives, were assessed to estimate the cost reduction per year. The improvements resulted in a reduction of inconclusive results and/or false-positives, without increasing false-negatives. For CH, false positives decreased by 26 per year with a related cost reduction of EUR 31,156. For CAH, 95 second heel punctures and seven false-positives per year were avoided, leading to a related cost reduction of EUR 7340. For MSUD, five false-positives per year were avoided with a related cost reduction of EUR 11,336. The improved screening algorithms led to a cost reduction of EUR 49,832 annually. Together with the known negative psychosocial effects associated with an inconclusive or false-positive NBS result, these results highlight the importance of improving NBS algorithms. Full article

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17 pages, 2084 KiB

Open AccessArticle

Newborn Screening for Sickle Cell Disease in Catalonia between 2015 and 2022—Epidemiology and Impact on Clinical Events

by José Manuel González de Aledo-Castillo, Ana Argudo-Ramírez, David Beneitez-Pastor, Anna Collado-Gimbert, Francisco Almazán Castro, Sílvia Roig-Bosch, Anna Andrés-Masó, Anna Ruiz-Llobet, Georgina Pedrals-Portabella, David Medina-Santamaria, Gemma Nadal-Rey, Marina Espigares-Salvia, Maria Teresa Coll-Sibina, Marcelina Algar-Serrano, Montserrat Torrent-Español, Pilar Leoz-Allegretti, Anabel Rodríguez-Pebé, Marta García-Bernal, Elisabet Solà-Segura, Amparo García-Gallego, Blanca Prats-Viedma, Rosa María López-Galera, Abraham J. Paredes-Fuentes, Sonia Pajares García, Giovanna Delgado-López, Adoración Blanco-Álvarez, Bárbara Tazón-Vega, Cristina Díaz de Heredia, María del Mar Mañú-Pereira, José Luis Marín-Soria, Judit García-Villoria, Pablo Velasco-Puyó and on behalf of the Sickle Cell Disease Newborn Screening Group of Catalonia Show full author list Hide full author list

Int. J. Neonatal Screen. 2024, 10(4), 69; https://doi.org/10.3390/ijns10040069 - 3 Oct 2024

Abstract

In 2015, Catalonia introduced sickle cell disease (SCD) screening in its newborn screening (NBS) program along with standard-of-care treatments like penicillin, hydroxyurea, and anti-pneumococcal vaccination. Few studies have assessed the clinical impact of introducing NBS programs on SCD patients. We analyzed the incidence [...] Read more.

In 2015, Catalonia introduced sickle cell disease (SCD) screening in its newborn screening (NBS) program along with standard-of-care treatments like penicillin, hydroxyurea, and anti-pneumococcal vaccination. Few studies have assessed the clinical impact of introducing NBS programs on SCD patients. We analyzed the incidence of SCD and related hemoglobinopathies in Catalonia and the change in clinical events occurring after introducing NBS. Screening 506,996 newborns from 2015 to 2022, we conducted a retrospective multicenter study including 100 screened (SG) and 95 unscreened (UG) SCD patients and analyzed SCD-related clinical events over the first six years of life. We diagnosed 160 cases of SCD, with an incidence of 1 in 3169 newborns. The SG had a significantly lower median age at diagnosis (0.1 y vs. 1.68 y, p < 0.0001), and initiated penicillin prophylaxis (0.12 y vs. 1.86 y, p < 0.0001) and hydroxyurea treatment earlier (1.42 y vs. 4.5 y, p < 0.0001). The SG experienced fewer median SCD-related clinical events (vaso-occlusive crisis, acute chest syndrome, infections of probable bacterial origin, acute anemia requiring transfusion, acute splenic sequestration, and pathological transcranial Doppler echography) per year of follow-up (0.19 vs. 0.77, p < 0.0001), a reduced number of annual emergency department visits (0.37 vs. 0.76, p < 0.0001), and fewer hospitalizations (0.33 vs. 0.72, p < 0.0001). SCD screening in Catalonia’s NBS program has effectively reduced morbidity and improved affected children’s quality of life. Full article

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9 pages, 212 KiB

Open AccessArticle

Prevalence and Mutation Analysis of Short-Chain acyl-CoA Dehydrogenase Deficiency Detected by Newborn Screening in Hefei, China

by Haili Hu, Qingqing Ma, Weidong Li, Yan Wang, Wangsheng Song and Yong Huang

Int. J. Neonatal Screen. 2024, 10(4), 68; https://doi.org/10.3390/ijns10040068 - 2 Oct 2024

Abstract

Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of mitochondrial fatty acid oxidation with highly variable biochemical and genetic characteristics. The present study aimed to estimate the prevalence and genetic characteristics of SCADD in newborns identified through screening. A total [...] Read more.

Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of mitochondrial fatty acid oxidation with highly variable biochemical and genetic characteristics. The present study aimed to estimate the prevalence and genetic characteristics of SCADD in newborns identified through screening. A total of 782,930 newborns were screened for SCADD in Hefei Neonatal Screening Center from January 2016 to December 2023. The blood samples from newborns were measured by tandem mass spectrometry (MS/MS). The suspected SCADD neonates were rechecked using next-generation gene sequencing for diagnosis. Sanger sequencing was used to verify the mutation site for patients with SCADD and their parents. A total of 21 SCADD cases were confirmed, with an incidence rate of 1/37,282. Genetic mutations were identified in all 21 cases, including 15 cases of compound heterozygous variation and 6 cases of homozygous variation. Twenty-one different mutation types and forty-two mutation sites were discovered, with the most frequent mutation being c.1031A>G, accounting for 21.43% (9/42), followed by c.1130C>T, accounting for 16.67% (7/42). Our findings expand the SCADD mutational spectra. c. 1031A>G and c.1130C>T are the common mutation sites for SCADD genes in newborns. SCADD diagnosed through NBS is primarily a benign condition, and early diagnosis is not necessarily essential. Full article

12 pages, 727 KiB

Open AccessArticle

A Novel Newborn Screening Program for Sickle Cell Disease in Nigeria

by Aisha A. Galadanci, Umma A. Ibrahim, Yvonne Carroll, Yusuf D. Jobbi, Zubaida L. Farouk, Aisha Mukaddas, Nafiu Hussaini, Bilya Sani Musa, Lauren J. Klein and Michael R. DeBaun

Int. J. Neonatal Screen. 2024, 10(4), 67; https://doi.org/10.3390/ijns10040067 - 30 Sep 2024

Abstract

Newborn screening for sickle cell disease (SCD) is sparse in sub-Saharan Africa. The leadership of the Aminu Kano Teaching Hospital (AKTH) in Kano, Nigeria, with the support of local religious authorities, established a groundbreaking SCD newborn screening program that has become the standard [...] Read more.

Newborn screening for sickle cell disease (SCD) is sparse in sub-Saharan Africa. The leadership of the Aminu Kano Teaching Hospital (AKTH) in Kano, Nigeria, with the support of local religious authorities, established a groundbreaking SCD newborn screening program that has become the standard of care for pregnant women and their newborns. Our program includes (1) prenatal genetic counseling for all pregnant women in the antenatal clinic, (2) newborn screening, (3) postnatal genetic counseling for parents of newborns diagnosed with SCD and SCT, and (4) referral of newborns with SCD for follow-up in the SCD Comprehensive Care Clinic by 3 months of age. From September 2020 to December 2023, the team screened 7530 infants for SCD at the AKTH, identifying 126 (1.7%) infants with SCD and 1546 (20.5%) with SCT. Of these, 93 (73.8%) newborns with SCD received individualized genetic counseling, and 43 (46%) were referred to the SCD Comprehensive Care Clinic before 3 months. Group genetic counseling was provided to the parents of 778 (50.3%) of newborns identified with SCT. The SCD newborn screening at the AKTH is now standard care, indicating the viability of sustaining an SCD newborn screening program that provides pre- and postnatal genetic counseling and comprehensive SCD care within a low-income setting. Full article

(This article belongs to the Special Issue A Lifespan Approach to Health and Well-Being Leveraging Neonatal Screening: Efforts in Advocacy, Academia, Research, and Clinical Care)

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2 pages, 177 KiB

Open AccessReply

Reply to Bouva et al. Comment on “Dijkstra et al. A False-Negative Newborn Screen for Tyrosinemia Type 1—Need for Re-Evaluation of Newborn Screening with Succinylacetone. Int. J. Neonatal Screen. 2023, 9, 66”

by Allysa M. Dijkstra, Kimber Evers-van Vliet, M. Rebecca Heiner-Fokkema, Frank A. J. A. Bodewes, Dennis K. Bos, József Zsiros, Koen J. van Aerde, Klaas Koop, Francjan J. van Spronsen and Charlotte M. A. Lubout

Int. J. Neonatal Screen. 2024, 10(4), 66; https://doi.org/10.3390/ijns10040066 - 24 Sep 2024

Abstract

We thank the authors for their comments [...] Full article

(This article belongs to the Special Issue Newborn Screening for Disorders of Amino Acid Metabolism)

2 pages, 147 KiB

Open AccessComment

Comment on Dijkstra et al. A False-Negative Newborn Screen for Tyrosinemia Type 1—Need for Re-Evaluation of Newborn Screening with Succinylacetone. Int. J. Neonatal Screen. 2023, 9, 66

by Marelle J. Bouva, Rose E. Maase and Ruurd M. van Elburg

Int. J. Neonatal Screen. 2024, 10(4), 65; https://doi.org/10.3390/ijns10040065 - 24 Sep 2024

Cited by 1

Abstract

The assessment of newborn screening (NBS) algorithms’ performance to ensure quality improvements is a continuous process: false-positive referrals can enable optimisations in the shorter term, but false-negative referrals are often only discovered many years after the screening has taken place [...] Full article

(This article belongs to the Special Issue Newborn Screening for Disorders of Amino Acid Metabolism)

11 pages, 832 KiB

Open AccessArticle

Charting the Ethical Frontier in Newborn Screening Research: Insights from the NBSTRN ELSI Researcher Needs Survey

by Yekaterina Unnikumaran, Mei Lietsch and Amy Brower

Int. J. Neonatal Screen. 2024, 10(3), 64; https://doi.org/10.3390/ijns10030064 - 19 Sep 2024

Abstract

From 2008 to 2024, the Newborn Screening Translational Research Network (NBSTRN), part of the National Institute of Child Health and Human Development (NICHD) Hunter Kelly Newborn Screening Program, served as a robust infrastructure to facilitate groundbreaking research in newborn screening (NBS), public health, [...] Read more.

From 2008 to 2024, the Newborn Screening Translational Research Network (NBSTRN), part of the National Institute of Child Health and Human Development (NICHD) Hunter Kelly Newborn Screening Program, served as a robust infrastructure to facilitate groundbreaking research in newborn screening (NBS), public health, rare disease, and genomics. Over its sixteen years, NBSTRN developed into a significant international network, supporting innovative research on novel technologies to screen, diagnose, treat, manage, and understand the natural history of more than 280 rare diseases. The NBSTRN tools and resources were used by a variety of stakeholders including researchers, clinicians, state NBS programs, parents, families, and policy makers. Resources and expertise for the newborn screening community in ethical, legal, and social issues (ELSI) has been an important area of focus for the NBSTRN and this includes efforts across the NBS system from pilot studies of candidate conditions to public health implementation of screening for new conditions, and the longitudinal follow-up of NBS-identified individuals to inform health outcomes and disease understanding. In 2023, the NBSTRN conducted a survey to explore ELSI issues in NBS research, specifically those encountered by the NBS community. Since NBS research involves collaboration among researchers, state NBS programs, clinicians, and families, the survey was broadly designed and disseminated to engage all key stakeholders. With responses from 88 members of the NBS community, including researchers and state NBS programs, the survey found that individuals rely most on institutional and collegial resources when they encounter ELSI questions. Most survey responses ranked privacy as extremely or very important in NBS research and identified the need for policies that address informed consent in NBS research. The survey results highlight the need for improved collaborative resources and educational programs focused on ELSI for the NBS community. The survey results inform future efforts in ELSI and NBS research in the United States (U.S.) and the rest of the world, including the development of policies and expanded ELSI initiatives and tools that address the needs of all NBS stakeholders. Full article

(This article belongs to the Special Issue Ethical and Psychosocial Aspects of Genomics in the Neonatal Period)

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International Journal of Neonatal Screening

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