International Journal of Neonatal Screening

13 pages, 787 KiB

Open AccessArticle

Newborn Screening for Congenital Heart Disease: A Five-Year Study in Shanghai

by Youping Tian, Qing Gu, Xiaojing Hu, Xiaoling Ge, Xiaojing Ma, Miao Yang, Pin Jia, Jing Zhang, Lulu Yang, Quming Zhao, Fang Liu, Ming Ye, Yulin Yang and Guoying Huang

Int. J. Neonatal Screen. 2025, 11(2), 38; https://doi.org/10.3390/ijns11020038 - 17 May 2025

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Abstract

This study aimed to report the progress and results of the newborn screening program for congenital heart disease (CHD) in south Shanghai between 2019 and 2023, and to evaluate the accuracy of the dual-index method (pulse oximetry (POX) plus cardiac murmur auscultation) in [...] Read more.

This study aimed to report the progress and results of the newborn screening program for congenital heart disease (CHD) in south Shanghai between 2019 and 2023, and to evaluate the accuracy of the dual-index method (pulse oximetry (POX) plus cardiac murmur auscultation) in clinical practice. Between 2019 and 2023, a total of 198,606 (99.89%) newborns were screened for CHD, of whom 3299 (1.66%) tested positive, 3043 (92.24%) underwent echocardiography for CHD diagnosis and 1109 were diagnosed with CHD in a timely manner. Among 195,307 infants with negative screening results using the dual-index method, 139 (0.07%) were later diagnosed with CHD, and none of these infants died. More than half of these false-negative infants (59.39%) were identified due to the detection of a heart murmur during routine physical examinations within six months after birth. Compared to POX testing alone, the dual-index method significantly improved the sensitivity of screening for CHD, and kept high specificity in clinical practice. This study demonstrated that newborn screening for CHD has been well conducted in Shanghai, and the dual-index method had high accuracy and reliability for neonatal CHD screening in clinical practice. Full article

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12 pages, 809 KiB

Open AccessArticle

Screening Blind Spot: Missing Preterm Infants in the Detection of Congenital Hypothyroidism

by Ashleigh Brown, Paul Hofman, Dianne Webster and Natasha Heather

Int. J. Neonatal Screen. 2025, 11(2), 37; https://doi.org/10.3390/ijns11020037 - 13 May 2025

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Abstract

Congenital hypothyroidism (CH) is a critical condition in infancy where early detection is vital for optimal development. This study aimed to evaluate the sensitivity of Aotearoa New Zealand’s Newborn Metabolic Screening “Low Birth Weight” protocol for detecting CH in preterm infants. A 10-year [...] Read more.

Congenital hypothyroidism (CH) is a critical condition in infancy where early detection is vital for optimal development. This study aimed to evaluate the sensitivity of Aotearoa New Zealand’s Newborn Metabolic Screening “Low Birth Weight” protocol for detecting CH in preterm infants. A 10-year audit was conducted on 2935 preterm infants (<2000 g or ≤34 weeks gestation) screened within NICUs or SCBUs in the Auckland region. The study assessed both screen-detected and clinically detected cases of CH. Data were collected from screening and clinical records to evaluate the sensitivity and reliability of the current protocol. The audit identified 19 cases of primary CH, with a 1:154 incidence. Thirteen cases met the criteria for inclusion in the audit. Just over half of the eligible cases (7/13) were screen-detected, while the remaining were detected clinically, suggesting limitations in screening sensitivity. The analysis revealed that the protocol missed permanent as well as transient cases, and that biochemical severity was not predictive of permanence. A revised screening protocol was developed and commenced in July 2024. Full article

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

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12 pages, 977 KiB

Open AccessArticle

Characterization of C5 Acylcarnitines and Related Dicarboxylic Acylcarnitines in Saudi Newborns: Screening, Confirmation, and Cutoff Variation

by Hanadi A. Bokhari, Ahmed H. Mujamammi, Huda A. Bader, Hannadi J. Alamri and Khalid K. Alharbi

Int. J. Neonatal Screen. 2025, 11(2), 36; https://doi.org/10.3390/ijns11020036 - 12 May 2025

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Abstract

Newborn screening (NBS) is a nationwide program for the early detection of disability in the Saudi population. This study focused on specific disorders related to organic acids that share C5 acylcarnitines derivatives and related dicarboxylic acylcarnitines as primary screening metabolites. We aimed to [...] Read more.

Newborn screening (NBS) is a nationwide program for the early detection of disability in the Saudi population. This study focused on specific disorders related to organic acids that share C5 acylcarnitines derivatives and related dicarboxylic acylcarnitines as primary screening metabolites. We aimed to determine the frequency of C5 acylcarnitine derivatives and related dicarboxylic acylcarnitines among screened newborns; confirm truly positive screening results using urine organic acid analysis; and compare the cutoff values for C5, C5DC, and C5OH acylcarnitines from the selected analytical centers. Data from laboratory positively screened and confirmed samples from the Public Health Authority (PHA) over 3 years were retrieved and analyzed to determine the frequency of the selected metabolites and percentage of true positive results among the positively screened samples. We identified significant correlations among variables such as disease, sex, and C5 metabolites across different cities. We clarified the frequency of true positive results for C5 acylcarnitine derivatives and related dicarboxylic acylcarnitines among Saudi newborns and highlighted significant variations in cutoff values across analytical centers. These findings contribute to the enhancement of NBS protocols and early intervention strategies. Full article

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16 pages, 1552 KiB

Open AccessArticle

Evaluation of the Performance of Newborn Screening for Tyrosinemia Type 1 in The Netherlands: Suggestions for Improvements Using Additional Biomarkers in Addition to Succinylacetone

by Marelle J. Bouva, Allysa M. Kuypers, Evelien A. Kemper, Rose E. Maase, Annet M. Bosch, Francjan J. van Spronsen, Annemieke C. Heijboer, M. Rebecca Heiner-Fokkema, Sandra G. Heil and Anita Boelen

Int. J. Neonatal Screen. 2025, 11(2), 35; https://doi.org/10.3390/ijns11020035 - 9 May 2025

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Abstract

Currently, Dutch newborns are screened for tyrosinemia type 1 (TT1) using succinylacetone (SA) as the biomarker. Although the sensitivity of the test is high, a high number of false positives is observed. Here, the aim is to evaluate the current Dutch newborn-screening protocol [...] Read more.

Currently, Dutch newborns are screened for tyrosinemia type 1 (TT1) using succinylacetone (SA) as the biomarker. Although the sensitivity of the test is high, a high number of false positives is observed. Here, the aim is to evaluate the current Dutch newborn-screening protocol and to assess alternatives, specifically the use of biomarkers that are already being measured, to increase the positive predictive value (PPV). TT1 screening was performed with the Revvity NeoBase assay between 2008 and 2017, and since 2018, the Revvity NeoBase 2 assay has been used. Data from 2018 to 2021 were used for evaluation. To simulate alternative screening protocols, these data were enriched with results of referrals from other periods and a false negative (FN) from 2010. In 2018–2021, 693,821 newborns were screened, resulting in 23 referrals, of whom two were TT1 patients. For this period, to date, no FN have been reported, resulting in a provisional sensitivity of 100%, a specificity of 99.997%, and a PPV and negative predictive value of 9% and 100%, respectively. To improve the PPV, we combined SA, tyrosine (tyr), tyr × SA and tyr/phenylalanine and achieved a PPV of 72% for this dataset without introducing FN in the original dataset. This illustrates that future screening for TT1 may benefit from the addition of these biomarkers. Full article

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12 pages, 237 KiB

Open AccessArticle

Newborn Screening for Gaucher Disease: The New Jersey Experience

by Caitlin Menello, Shaney Pressley, Madeline Steffensen, Sarah Schmidt, Helio Pedro, Reena Jethva, Karen Valdez-Gonzalez, Darius J. Adams, Punita Gupta, Lorien Tambini King, Milen Velinov, Sharon Anderson, Peyman Bizargity, Beth Pletcher, Allysa Tuite, Christina Kresge, Debra Lynn Day-Salvatore, Ryan Kuehl and Can Ficicioglu

Int. J. Neonatal Screen. 2025, 11(2), 34; https://doi.org/10.3390/ijns11020034 - 2 May 2025

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Abstract

Gaucher disease (GD) is a lysosomal storage disorder (LSD) characterized by glycosphingolipid accumulation. Age of symptomonset and disease progression varies across types of disease. Newborn screening (NBS) for Gaucher disease facilitates early identification of affected individuals and enables pre-symptomatic monitoring with the goal [...] Read more.

Gaucher disease (GD) is a lysosomal storage disorder (LSD) characterized by glycosphingolipid accumulation. Age of symptomonset and disease progression varies across types of disease. Newborn screening (NBS) for Gaucher disease facilitates early identification of affected individuals and enables pre-symptomatic monitoring with the goal of starting therapies early and improving clinical outcomes. This multi-center study involved New Jersey NBS referral centers. Data regarding initial NBS results, confirmatory testing, diagnosis, and treatment were collected. For patients on therapy, monitoring biomarkers and exam findings are available as of the last clinical evaluation. Between July 2019 and December 2023, 438,515 newborns were screened, with 60 screen-positive cases. Of those positive screens, 19 cases with positive screens did not undergo confirmatory testing due to parental refusal, loss to follow-up, or death; 23 cases were false positives; 14 newborns were diagnosed with GD type I; 2 newborns were diagnosed with suspected type I GD; 2 newborns were diagnosed with GD type II; and 1 case is still pending. Three type I GD patients started enzyme replacement therapy, with the youngest starting at 28 months of age. Post-treatment data are available for these individuals. One type II case was referred to experimental gene therapy, and one was started on ERT. Our results demonstrate that NBS for GD is a valuable public health tool that can facilitate early diagnosis and intervention. Full article

12 pages, 1057 KiB

Open AccessArticle

Characteristic Findings of Infants with Transient Elevation of Acylcarnitines in Neonatal Screening and Neonatal Weight Loss

by Sakura Morishima, Yumi Shimada, Yoriko Watanabe and Kenji Ihara

Int. J. Neonatal Screen. 2025, 11(2), 33; https://doi.org/10.3390/ijns11020033 - 29 Apr 2025

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Abstract

The detection of elevated long-chain acylcarnitine levels, particularly C14:1 and the C14:1/C2 ratio, during neonatal screening may indicate very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), although similar findings can result from postnatal starvation. We investigated the relationship between false-positive results, postnatal weight loss, and subsequent [...] Read more.

The detection of elevated long-chain acylcarnitine levels, particularly C14:1 and the C14:1/C2 ratio, during neonatal screening may indicate very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), although similar findings can result from postnatal starvation. We investigated the relationship between false-positive results, postnatal weight loss, and subsequent growth. Additionally, we explored potential diagnostic markers of postnatal starvation. The following neonates from Oita Prefecture (April 2014–March 2024) were included in this study: patients identified as false-positive for VLCADD (n = 19), patients with VLCADD (n = 3), and children negative in mass screening who completed their 3-year-old health check-up (n = 30). The false-positive group exhibited significant weight loss at blood sampling for neonatal screening. An acylcarnitine analysis showed significant increases in various short- to long-chain fatty acids in the false-positive group, likely owing to enhanced fatty acid catabolism via β-oxidation. Elevation of a broad range of fatty acids and reduced amino acid levels seemed to be associated with significant weight loss at blood sampling. Full article

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15 pages, 893 KiB

Open AccessArticle

An Explorative Qualitative Study of the Role of a Genetic Counsellor to Parents Receiving a Diagnosis After a Positive Newborn Bloodspot Screening

by Samantha A. Sandelowsky, Alison McEwen, Jacqui Russell, Kirsten Boggs, Rosie Junek, Carolyn Ellaway, Arthavan Selvanathan, Michelle A. Farrar and Kaustuv Bhattacharya

Int. J. Neonatal Screen. 2025, 11(2), 32; https://doi.org/10.3390/ijns11020032 - 28 Apr 2025

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Abstract

Newborn Bloodspot Screening (NBS) can detect severe treatable health conditions with onset during infancy. The parents of a newborn baby are vulnerable in the days after birth, and the optimal way to deliver the shocking and distressing news of a potential serious diagnosis [...] Read more.

Newborn Bloodspot Screening (NBS) can detect severe treatable health conditions with onset during infancy. The parents of a newborn baby are vulnerable in the days after birth, and the optimal way to deliver the shocking and distressing news of a potential serious diagnosis is yet to be defined. More data are needed to determine whether access to a genetic counsellor (GC) improves families’ experiences with genetic conditions identified by NBS. This study aimed to explore the similarities and differences for parents who received a positive NBS result for Spinal Muscular Atrophy (SMA) and received access to a GC (GC cohort), to a cohort of parents who received a diagnosis for inborn errors of metabolism (IEM) and did not have access to a GC (non-GC cohort). Semi-structured interviews explored the retrospective experiences of receiving the NBS result, including diagnosis implications and subsequent adaptation to respective genetic diagnoses. Inductive thematic analysis was used from group comparison. 7 SMA families and 5 IEM families were included in the study. Four themes were identified: 1. minimal pre-test counselling; 2. perceived lack of local healthcare team knowledge; 3. enabling factors for adaptation; 4. implications for both individuals and their families. Both the GC and non-GC cohorts reported insufficient counselling in the pre-test period and described feeling traumatised at the time of the diagnosis delivery. Families without subsequent GC input described limited understanding of the disease due to the use of medicalized terms, as well as a decreased understanding of reproductive options, familial communication and subsequent cascade screening. GCs can support information needs and adaptation following a NBS diagnosis. Full article

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16 pages, 1489 KiB

Open AccessArticle

Expanded Newborn Screening in Italy: The First Report of Lombardy Region

by Clarissa Berardo, Alessandra Vasco, Alessia Mauri, Simona Lucchi, Laura Cappelletti, Laura Saielli, Manuela Rizzetto, Davide Biganzoli, Cristina Montrasio, Diana Postorivo, Elisa Pratiffi, Andrea Meta, Stephana Carelli, Alessandro Amorosi, Sabrina Paci, Graziella Cefalo, Francesca Furlan, Francesca Menni, Serena Gasperini, Viola Crescitelli, Giuseppe Banderali, Gianvincenzo Zuccotti, Luisella Alberti and Cristina Cereda Show full author list Hide full author list

Int. J. Neonatal Screen. 2025, 11(2), 31; https://doi.org/10.3390/ijns11020031 - 25 Apr 2025

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Abstract

Background: Newborn screening (NBS) is a preventive healthcare program aiming at identifying the inborn errors of metabolism (IEMs) in asymptomatic infants to reduce the risk of severe complications. The aim of this study was to report the first years (2016–2020) of the expanded [...] Read more.

Background: Newborn screening (NBS) is a preventive healthcare program aiming at identifying the inborn errors of metabolism (IEMs) in asymptomatic infants to reduce the risk of severe complications. The aim of this study was to report the first years (2016–2020) of the expanded NBS program in the Lombardy region, Italy. Methods: Dried blood spots were collected from newborns’ heels at 48–72 h after birth. FIA-MS/MS was performed to evaluate specific biochemical markers. Genetic confirmation was achieved via Sanger or NGS on newborns and reported to a clinical reference center (CRC). Results: A total of 343,507 newborns were tested; 1414/343,507 resulted as positive to NBS and were reported to the CRC. A total of 209 newborns were diagnosed with IEMs: 206 infants received a diagnosis of IEM through NBS, confirmed by genetic analysis; three neonates were not positive to NBS but were subsequentially diagnosed with IEMs. A total of 1208/343,507 were false positive cases. Twenty-seven types of IEMs were diagnosed in 209 patients: 111 newborns were affected by aminoacidemias, 11 by urea cycle disorders, 27 by organic acidemias, 34 by fatty acid oxidation disorders, and 26 by secondary conditions. Conclusions: We report here for the first time the IEM incidence and distribution in the Lombardy region in the first five years of NBS. Full article

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16 pages, 4740 KiB

Open AccessArticle

Newborn Screening for Metachromatic Leukodystrophy in Tuscany: The Paradigm of a Successful Preventive Medicine Program

by Sabrina Malvagia, Alessandra Bettiol, Margherita Porcaro, Massimo Mura, Silvia Funghini, Daniela Ombrone, Giulia Forni, Emanuela Scolamiero, Filippo Coppi, Roberta Damiano, Cristina Cereda, Simonetta Simonetti, Annalisa Lonetti, Marta Daniotti, Anna Caciotti, Amelia Morrone, Valeria Calbi, Francesca Fumagalli, Alessandro Aiuti, Elena Procopio, Renzo Guerrini and Giancarlo la Marca Show full author list Hide full author list

Int. J. Neonatal Screen. 2025, 11(2), 30; https://doi.org/10.3390/ijns11020030 - 24 Apr 2025

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Abstract

Metachromatic leukodystrophy (MLD) is a rare inherited disorder of lysosomal storage, caused by a deficiency in the arylsulfatase A (ARSA) enzyme, leading to toxic accumulation of sulfatides, which progressively impair motor and cognitive function. MLD is a candidate for inclusion in newborn screening [...] Read more.

Metachromatic leukodystrophy (MLD) is a rare inherited disorder of lysosomal storage, caused by a deficiency in the arylsulfatase A (ARSA) enzyme, leading to toxic accumulation of sulfatides, which progressively impair motor and cognitive function. MLD is a candidate for inclusion in newborn screening (NBS) programs, due to the narrow pre-symptomatic window for effective therapeutic intervention. We set up a prospective pilot NBS program for MLD in Tuscany, based on a two-step approach. The first-tier test quantified four sulfatides; if levels exceeded the cut-off, we performed the second-tier test by measuring ARSA activity on the same neonatal dried blood spot (DBS). We performed the first-tier test on 42,262 newborns over two years and the second-tier test on residual neonatal DBS from 90 of them (0.21%). We recalled 10 newborns (0.02%) for an additional DBS, due to insufficient residual material for a second-tier test (n = 4) or to low ARSA activity (n = 6). We found normal ARSA activity in all new DBS and identified no new cases of MLD. Retrospective analysis of eight neonatal and fifteen non-neonatal DBS from patients with genetically confirmed MLD showed that the algorithm accurately identified MLD patients. This diagnostic algorithm proved feasible and accurate for early detection of MLD in prospective NBS. Full article

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13 pages, 3572 KiB

Open AccessArticle

Results of the Hungarian Newborn Screening Pilot Program for Spinal Muscular Atrophy

by Krisztina Hegedűs, István Lénárt, Andrea Xue, Péter Béla Monostori, Ákos Baráth, Borbála Mikos, Szabolcs Udvari, Adrienn Géresi, Attila József Szabó, Csaba Bereczki, Mária Judit Molnár and Ildikó Szatmári

Int. J. Neonatal Screen. 2025, 11(2), 29; https://doi.org/10.3390/ijns11020029 - 23 Apr 2025

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Abstract

The growing need to identify spinal muscular atrophy (SMA) patients as early as possible has shifted attention to newborn screening (NBS). The aim of the present study was to evaluate the possibility of including the SMA-NBS in the Hungarian screening panel. As the [...] Read more.

The growing need to identify spinal muscular atrophy (SMA) patients as early as possible has shifted attention to newborn screening (NBS). The aim of the present study was to evaluate the possibility of including the SMA-NBS in the Hungarian screening panel. As the first step, a government-funded pilot program started in November 2022 and continued until the end of 2023. Evaluation of the first 14 months was followed by the decision to lengthen the program until the end of 2024, which was further supported by the needs of society. Screening tests were performed in both Hungarian national screening laboratories uniformly using the combined EONIS SCID-SMA real-time PCR assay kit by Revvity, for the newborns whose parents gave written consent for the analysis. Altogether, 155,985 newborns were screened during the 26 months of the program, which was 87% of all newborns involved in the national neonatal screens of the same period. All 19 newborns identified on the screen were diagnosed with SMA, confirmed by a multiplex ligation-dependent probe amplification assay (MLPA). The favorable results of the pilot study support the inclusion of the SMA in the national screening panel at the earliest possible date. Full article

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1 pages, 139 KiB

Open AccessCorrection

Correction: Donnelly et al. A Case of DNAJC12-Deficient Hyperphenylalaninemia Detected on Newborn Screening: Clinical Outcomes from Early Detection. Int. J. Neonatal Screen. 2024, 10, 7

by Colleen Donnelly, Lissette Estrella, Ilona Ginevic and Jaya Ganesh

Int. J. Neonatal Screen. 2025, 11(2), 28; https://doi.org/10.3390/ijns11020028 - 23 Apr 2025

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In the original publication [...] Full article

11 pages, 843 KiB

Open AccessCommentary

India: The Last and Best Frontier for Cystic Fibrosis Newborn Screening with Perspectives on Special Challenges

by Philip M. Farrell, Grace R. Paul and Sneha D. Varkki

Int. J. Neonatal Screen. 2025, 11(2), 27; https://doi.org/10.3390/ijns11020027 - 17 Apr 2025

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Abstract

Because a delayed diagnosis of cystic fibrosis (CF) is detrimental and may be fatal, screening at birth has become routine in the Western world and has proven beneficial for many reasons, in addition to enabling prompt specialized care. Newborn screening (NBS) programs have [...] Read more.

Because a delayed diagnosis of cystic fibrosis (CF) is detrimental and may be fatal, screening at birth has become routine in the Western world and has proven beneficial for many reasons, in addition to enabling prompt specialized care. Newborn screening (NBS) programs have elucidated the true incidence of CF in a variety of populations and enabled rapid genotype identification through the analysis of the cystic fibrosis transmembrane regulator (CFTR) gene. NBS studies also have revealed regional and population differences in CFTR variants and refuted the dogma that CF is a “white person’s disease”. But some regions have not yet implemented CF NBS, particularly in Asia where the disease prevalence has been uncertain. While the needs of a few low-and-middle-income countries are being addressed sequentially, one of the regions of greatest current interest is the Indian subcontinent because of recent data suggesting a higher incidence than that previously assumed, and clinical observations indicating tragic outcomes due to delayed diagnoses or failure to diagnose the disorder in young children. Thus, we conclude that the opportunities for research combined with service in the Indian subcontinent are urgent and potentially very impactful. Consequently, India is the last and best frontier for CF NBS, as we argue herein. Full article

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

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14 pages, 1182 KiB

Open AccessArticle

The Establishment of Expanded Newborn Screening in Rural Areas of a Developing Country: A Model from Health Regions 7 and 8 in Thailand

by Khunton Wichajarn, Nopporn Sawatjui, Prinya Prasongdee, Amrin Panklin, Kanda Sornkayasit, Natchita Chungkanchana, Supharada Tessiri, Preawwalee Wintachai, Sumalai Dechyotin, Chalanda Pasomboon, Jilawaporn Ratanapontee, Sureerat Thanakitsuwan and Aree Rattanathongkom

Int. J. Neonatal Screen. 2025, 11(2), 26; https://doi.org/10.3390/ijns11020026 - 12 Apr 2025

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Abstract

Expanded newborn screening (NBS) programs are essential for early detection and treatment. This study highlights the implementation of an expanded NBS program for inborn errors of metabolism (IEMs) and congenital hypothyroidism (CH) in rural Thailand, focusing on Health Regions 7 and 8 as [...] Read more.

Expanded newborn screening (NBS) programs are essential for early detection and treatment. This study highlights the implementation of an expanded NBS program for inborn errors of metabolism (IEMs) and congenital hypothyroidism (CH) in rural Thailand, focusing on Health Regions 7 and 8 as a model for resource-limited settings. Using the KKU-IEM web-based platform, the program streamlined workflows, integrating logistics, real-time sample tracking, and electronic data management. Regular training sessions, continuous feedback, and systematic monitoring improved outcomes. Starting from October 2022, the program covered 98.6% of 123,692 live births, identifying 101 CH cases (1 in 1208 live births) and 20 IEM cases (1 in 6100 live births). The CH incidence was slightly higher than Thailand’s national average, while the IEM incidence was double that found in a previous Bangkok pilot study. Six cases highlighted maternal conditions affecting outcomes. Process improvements reduced the average reporting time from 9.13 days in 2023 to 8.4 days in 2024, with a 19% reduction in Bueng Kan Province. Efficiencies were driven by electronic ordering, real-time tracking, and stakeholder collaboration. This program demonstrates a scalable model for rural settings, emphasizing technology integration, collaboration, and quality control. Future efforts should refine diagnostics, expand disease coverage, and enhance long-term outcomes. Full article

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18 pages, 885 KiB

Open AccessCase Report

Rethinking Newborn Screening: A Case of GALM Deficiency

by Eva M. M. Hoytema van Konijnenburg, Silvia Radenkovic, Klaas Koop, Hubertus C. M. T. Prinsen and Monique de Sain-van der Velden

Int. J. Neonatal Screen. 2025, 11(2), 25; https://doi.org/10.3390/ijns11020025 - 11 Apr 2025

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Abstract

Galactosemia is a group of hereditary disorders of galactose metabolism. A new type of galactosemia was discovered, caused by a deficiency in galactose mutarotase (GALM), which catalyzes the epimerization between beta- and alpha-D-galactose. All GALM-deficient patients reported in the literature (n = 44) [...] Read more.

Galactosemia is a group of hereditary disorders of galactose metabolism. A new type of galactosemia was discovered, caused by a deficiency in galactose mutarotase (GALM), which catalyzes the epimerization between beta- and alpha-D-galactose. All GALM-deficient patients reported in the literature (n = 44) had abnormal newborn screening (NBS) results or did not receive NBS (n = 2). We present the first patient with GALM deficiency who had negative NBS in the Netherlands and was identified at age 1.5 years during broad metabolic screening because of her global developmental delay, nystagmus, and a history of jaundice. Biochemical evaluation showed a significantly increased excretion of galactose (13,167 mmol/mol creatinine, upper limit of normal (ULN) 326) and galactitol (427 mmol/mol creatinine, ULN 71). Whole exome sequencing showed homozygous variants in GALM (c.424G>A p.(Gly142Arg)). A galactose-restricted diet was started, resulting in biochemical normalization. We present a comprehensive review of GALM-deficient patients, NBS data, and treatment. Different designs of galactosemia screening may lead to overlooking patients with GALM deficiency. Although the effects of lactose-restricted diet are largely unknown, a diet might prevent cataract in some patients. Full article

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22 pages, 1424 KiB

Open AccessGuidelines

Cystic Fibrosis Newborn Screening: A Systematic Review-Driven Consensus Guideline from the United States Cystic Fibrosis Foundation

by Meghan E. McGarry, Karen S. Raraigh, Philip Farrell, Faith Shropshire, Karey Padding, Cambrey White, M. Christine Dorley, Steven Hicks, Clement L. Ren, Kathryn Tullis, Debra Freedenberg, Q. Eileen Wafford, Sarah E. Hempstead, Marissa A. Taylor, Albert Faro, Marci K. Sontag and Susanna A. McColley

Int. J. Neonatal Screen. 2025, 11(2), 24; https://doi.org/10.3390/ijns11020024 - 2 Apr 2025

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Newborn screening for cystic fibrosis (CF) has been universal in the US since 2010; however, there is significant variation among newborn screening algorithms. Systematic reviews were used to develop seven recommendations for newborn screening program practices to improve timeliness, sensitivity, and equity in [...] Read more.

Newborn screening for cystic fibrosis (CF) has been universal in the US since 2010; however, there is significant variation among newborn screening algorithms. Systematic reviews were used to develop seven recommendations for newborn screening program practices to improve timeliness, sensitivity, and equity in diagnosing infants with CF: (1) The CF Foundation recommends the use of a floating immunoreactive trypsinogen (IRT) cutoff over a fixed IRT cutoff; (2) The CF Foundation recommends using a very high IRT referral strategy in CF newborn screening programs whose variant panel does not include all CF-causing variants in CFTR2 or does not have a variant panel that achieves at least 95% sensitivity in all ancestral groups within the state; (3) The CF Foundation recommends that CF newborn screening algorithms should not limit CFTR variant detection to the F508del variant or variants included in the American College of Medical Genetics-23 panel; (4) The CF Foundation recommends that CF newborn screening programs screen for all CF-causing CFTR variants in CFTR2; (5) The CF Foundation recommends conducting CFTR variant screening twice weekly or more frequently as resources allow; (6) The CF Foundation recommends the inclusion of a CFTR sequencing tier following IRT and CFTR variant panel testing to improve the specificity and positive predictive value of CF newborn screening; (7) The CF Foundation recommends that both the primary care provider and the CF specialist be notified of abnormal newborn screening results. Through implementation, it is anticipated that these recommendations will result in improved sensitivity, equity, and timeliness of CF newborn screening, leading to improved health outcomes for all individuals diagnosed with CF following newborn screening and a decreased burden on families. Full article

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

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7 pages, 197 KiB

Open AccessArticle

A Review of Newborn Screening for VLCADD: The Wisconsin Experience

by Breanna Mitchell, Jessica Scott-Schwoerer, Ashley Kuhl, Kristina Garcia and Patrice Held

Int. J. Neonatal Screen. 2025, 11(2), 23; https://doi.org/10.3390/ijns11020023 - 26 Mar 2025

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Abstract

Very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is due to a defect in metabolism of long-chain fatty acids. Infants with VLCADD may experience cardiomyopathy, hypoglycemia, or even death; thus, early detection and intervention is crucial. The spectrum of disease and natural variation in newborn metabolism, [...] Read more.

Very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is due to a defect in metabolism of long-chain fatty acids. Infants with VLCADD may experience cardiomyopathy, hypoglycemia, or even death; thus, early detection and intervention is crucial. The spectrum of disease and natural variation in newborn metabolism, however, lead to overlap in acylcarnitine values between affected and unaffected individuals, which contributes to the difficulty in identifying true positive cases while minimizing false positive cases. VLCADD was added to the state of Wisconsin’s newborn screening (NBS) panel in 2000. A previous retrospective review of VLCADD screen positive cases identified between 2000 and 2014 resulted in a change to the screening algorithm. Following implementation, a reduction in the percentage of false positive screens from 25.3% to 20.4% was observed between 2015 and 2021. The overall PPV also decreased, from 37.2% to 28%, due to an increase in the number of carriers identified (27.5% of cases in 2000–2014 and 51.8% of cases in 2015–2021). A data review also identified three long-chain acylcarnitine elevations (C14:1, C14:1/C16, and C14:1/C2) that had statistically significant differences in concentrations in true positive populations versus false positive populations. Utilization of the C14:1, C14:1/C16, and C14:1/C2 values in newborn screening may provide clearer distinction between true positive and carrier populations and additionally increase the PPV of this screen. Full article

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Int. J. Neonatal Screen., Volume 11, Issue 2 (June 2025) – 16 articles

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