International Journal of Neonatal Screening

10 pages, 564 KiB

Open AccessArticle

The Promising Role of Intestinal Organoids in the Diagnostic Work-Up of Cystic Fibrosis Screen Positive Inconclusive Diagnosis/CFTR-Related Metabolic Syndrome (CFSPID/CRMS)

by Noelia Rodriguez Mier, Marlies Destoop, Sacha Spelier, Anabela Santo Ramalho, Jeffrey M. Beekman, François Vermeulen, Karin M. de Winter-de Groot and Marijke Proesmans

Int. J. Neonatal Screen. 2025, 11(3), 52; https://doi.org/10.3390/ijns11030052 - 11 Jul 2025

Abstract

Cystic Fibrosis Screen Positive Inconclusive Diagnosis/CFTR-related Metabolic Syndrome (CFSPID/CRMS) presents a significant clinical challenge due to its variable diagnostic outcomes and uncertain disease progression. Current diagnostic strategies, including sweat chloride testing and genetic analysis fall short in delivering clear guidance for clinical decision-making and risk assessment. Here, we comment on the potential of CFTR functional tests in patient-derived intestinal organoids (PDIOs) to enhance early risk stratification in CFSPID/CRMS cases. Using four hypothetical cases based on real-world data, we illustrate diverse clinical trajectories: diagnosis of cystic fibrosis (CF), reclassification as a CFTR-related disorder (CFTR-RD), non-CF designation, and persistent diagnostic uncertainty. Organoid-based assays—such as forskolin-induced swelling (FIS), steady-state lumen area (SLA) analysis, and rectal organoid morphology analysis (ROMA)—offer functional insights into CFTR activity and drug responsiveness. Compared to existing CFTR functional tests, such as Intestinal Current Measurement (ICM) and Nasal Potential Difference (NPD), these assays are more accessible, highly reproducible, and when needed support personalized medicine approaches. PDIO-based assays could help identify infants at high risk of disease progression, facilitating earlier interventions while minimizing unnecessary follow-ups for those unlikely to develop CF-related symptoms. Although not yet widely implemented, these assays hold promise for refining CFSPID diagnostics and management. Future research should focus on establishing standardized protocols allowing validation of clinical utility. Full article

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

12 pages, 1564 KiB

Open AccessArticle

Training Primary Healthcare Professionals for Expanded Newborn Screening with Tandem Mass Spectrometry: Challenges for Community Genetics in Brazil

by Luzivan Costa Reis, Tassia Tonon, Marina Bernardes Acosta, Simone Martins de Castro, Vivian de Lima Spode Coutinho, Débora Gusmão Melo and Ida Vanessa Doederlein Schwartz

Int. J. Neonatal Screen. 2025, 11(3), 51; https://doi.org/10.3390/ijns11030051 - 30 Jun 2025

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Abstract

In Brazil, dried blood spots (DBSs) for newborn screening (NBS) should be collected between the 3rd and 5th days of life at local Basic Health Units (BHUs). This study reports the experience of face-to-face training at BHUs in southern Brazil during a pilot study for tandem mass spectrometry (MS/MS) inclusion in the NBS program. The pilot project involved screening for 22 inborn errors of metabolism (IEMs). The professionals at the BHUs were instructed to carry out the following: (a) explain the study to parents or guardians; (b) collect additional DBS samples on a different collection card (research card); and (c) deliver results to families. In-person visits were conducted at all 137 BHUs. These visits included an overview of the pilot project and distribution of educational materials, including a list of the 22 IEMs and informational leaflets on MS/MS-based NBS. Among the 486 healthcare professionals who participated, 91.2% were women. Overall, 97.1% of the BHUs reported being satisfied with the project. Questions regarding IEMs were raised in 40.1% of BHUs, and 13.1% reported complaints about the research card due to its lighter texture and drying difficulty. Training primary healthcare professionals in IEMs remains an urgent priority in Brazil, particularly in the context of expanded NBS using MS/MS, since they are the frontline professionals in the NBS program. Full article

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18 pages, 5349 KiB

Open AccessArticle

Qatar’s National Expanded Metabolic Newborn Screening Program: Incidence and Outcomes

by Tala Jamaleddin, Karen El-Akouri, Sumaya Abiib, Rola Mitri, Mamatha Ramaswamy, Sara Musa, Rehab Ali, Noora Shahbeck, Hilal Al Rifai, Ghassan Abdoh, Tawfeg Ben-Omran, Osama Y. Al-Dirbashi and Mashael Al-Shafai

Int. J. Neonatal Screen. 2025, 11(3), 50; https://doi.org/10.3390/ijns11030050 - 30 Jun 2025

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Abstract

Background: Newborn screening is an essential public health strategy that aims to detect a range of conditions, including inborn errors of metabolism, in neonates shortly after birth. The timely identification is crucial due to the asymptomatic nature of many conditions at birth, but which can lead to significant health complications if left untreated. Through this study, we aimed to investigate the incidence of IEMs screened by the Qatar National Newborn Screening Program. Methods: We retrospectively analyzed a total of 351,223 newborns screened from 2010 to 2023. The incidence for the studied IEMs was calculated and correlated with demographics, consanguinity, and family history. In addition, the diagnostic yield of different tests utilized was assessed. Results: Our study revealed a total of 318 positive cases with IEMs, and a significantly high incidence of 1:1105 for IEMs in Qatar. Classical Homocystinuria was the most frequently detected condition, with a cumulative incidence of 1:6754 live births, linked to the founder variant p. Arg336Cys in the CBS gene. Aminoacidopathies were the most prevalent category, followed by fatty acid oxidation disorders, organic acidurias, biotinidase deficiency, and urea cycle disorders. Genetic testing showed a high diagnostic yield of 90%. Of the 60 cases that underwent targeted variant testing, 98% were confirmed, while 90% of the 59 cases tested by single gene testing were confirmed. Conclusions: Our study provides the incidence rates of IEMs in Qatar and novel insights that could facilitate setting up/developing IEM incidence-reducing strategies and improving outcomes for affected newborns and their families. Full article

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3 pages, 165 KiB

Open AccessCorrection

Correction: Hall et al. Oral and Poster Abstracts of the 13th ISNS European Regional Meeting. Int. J. Neonatal Screen. 2025, 11, 21

by Kate Hall, Peter C. J. I. Schielen and Dimitris Platis

Int. J. Neonatal Screen. 2025, 11(3), 49; https://doi.org/10.3390/ijns11030049 - 24 Jun 2025

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Abstract

The authors wish to make the following correction to their paper published in the International Journal of Neonatal Screening [...] Full article

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Int. J. Neonatal Screen., Volume 11, Issue 3 (September 2025) – 4 articles

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