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Even though digital media use in early childhood has increased, compliance estimates vary depending on the screen time guideline applied. This study compared Portuguese, World Health Organization, and American Academy of Pediatrics recommendations within the same population, and examined factors associated with exceeding age-specific limits. Baseline data from 940 children aged two to six years (mean 4.67 ± 1.03; 52.8% boys) were analyzed. The mean daily screen time was 126 minutes. The exceedance prevalence and severity were classified according to each framework. Most children exceeded recommendations across all systems, with highest prevalence and severity under the Portuguese Society of Neuropediatrics, followed by the American Academy of Pediatrics and the World Health Organization. Despite systematic reclassification across guidelines, consistent determinants emerged: earlier age at first exposure (ORs ranging between 0.93 - 0.98), child Internet use (non-use: ORs between 0.06 - 0.38), higher maternal screen time (ORs between 1.02 - 1.04), and bedroom device access (ORs between 0.17 - 0.50) were associated with higher odds of exceeding limits. Parental awareness of recommendations was generally high, but quantitative restrictions were less consistently implemented. The findings suggest that prevalence estimates strongly depend on the guideline framework applied, while family-level determinants of excessive exposure remain stable across classification systems.

Rare diseases (RDs), affecting fewer than 5 people per 10,000, present unique challenges to usual care pathways due to their unique characteristics: rarity and large number of disease entities, heterogeneous clinical manifestations and genetic causes, multisystemic involvement, and high complexity of diagnosis and treatment. This complexity often hampers the setting of appropriate pathways of care, which are not easily identifiable by patients and stakeholders. This ultimately leads to significant delays in diagnosis, lack of timely access to RD treatments and profound inequalities across countries. To overcome these difficulties, European Reference Networks (ERNs) were established in 2017 to facilitate patients' referral to expertise and excellent services, aiming to reduce disparities and expedite diagnosis, standard of care, and treatment for people living with rare diseases (PLWRDs). Since 72% of rare diseases are of genetic in origin and mostly affect children, genomic newborn screening (gNBS) offers a powerful tool to overcome diagnostic barriers by providing early and accurate genetic diagnoses for a wide range of treatable pediatric RDs. Several gNBS initiatives have been implemented across Europe and worldwide. Screen4Care (S4C) is an EU-IHI funded research project integrating gNBS with artificial intelligence (AI)-based tools to improve care for PLWRDs in the EU. The project will offer gNBS to up to 18,000 infants using a capture-based panel (TREAT-panel) targeting 245 genes associated with treatable genetic disorders [ClinicalTrials.gov NCT06549218]. Within this framework, an operational pipeline and a comprehensive step-by-step process in collaboration with ERNs were developed to refer gNBS-positive newborns to the appropriate ERN, ensuring timely access to optimal standards of care and available treatments. We suggest that this organisational and structured health model might be adopted by EU Member States (MS), as it provides a defined clinical framework for identifying newborns with RDs at birth and ensuring they receive the correct care, thereby promoting patient-centred and equitable disease management.

Deficiency of adenosine deaminase 2 (DADA2) is an autoinflammatory disease with diverse phenotypes. We describe the genetics, phenotypes, and treatment of n = 48 DADA2 patients from Germany, Austria, and Switzerland. We report a high incidence of hematological (83%) and immunological features (85%), a comparatively low anti-tumor necrosis factor full-response rate (58%), and a high decision probability (21%) for hematopoietic cell transplantation (HCT). We establish a correlation between genetic variant ADA2 activity and patient ADA2 activity. Remarkably, lower patient ADA2 activity is predictive of neutropenia and shows a trend toward HCT decision, whereas higher patient ADA2 activity is predictive of vasculitis symptoms. Genetic variants with low residual ADA2 activity are significantly more common among patients receiving HCT. Our study corroborates previous observations connecting ADA2 activity and clinical phenotype, which up to now have been mainly based on in vitro data.

Pediatric clinically isolated syndrome (CIS) is the first inflammatory demyelinating event of the central nervous system and may progress to multiple sclerosis (MS). Data on relapse patterns and predictors of MS conversion in children remain limited. To evaluate the clinical, radiological, and immunological characteristics of pediatric CIS and to identify factors associated with relapse and final diagnosis. In this retrospective cohort study, pediatric patients (3-18 years) presenting with a first demyelinating event between 2011 and 2021 were included if follow-up was &#x2265;6 months. Clinical, MRI, laboratory, and immunological data were reviewed. Group comparisons were performed using non-parametric tests. Relapse predictors were explored using penalized logistic regression. A total of 26 patients were included (mean age 13.2&#x2009;&#xb1;&#x2009;3.2 years; 14 male). Optic neuritis was the most common presentation (57.7%). During a mean follow-up of 1.28&#x2009;&#xb1;&#x2009;1.31 years, 30.8% were diagnosed with MS. Relapse occurred in 42% of patients and differed significantly across diagnostic groups (p&#x2009;<&#x2009;0.001). EDSS scores improved significantly at 3 months (mean reduction 1.79&#x2009;&#xb1;&#x2009;0.92; p&#x2009;<&#x2009;0.001). NMO/MOG seropositivity was associated with final diagnosis (p&#x2009;=&#x2009;0.015). Oligoclonal band positivity showed an increased odds ratio for relapse (OR 7.22) but was not statistically significant. No independent relapse predictors were identified. Approximately one-third of pediatric CIS patients converted to MS. Relapse patterns differed across diagnostic groups. Although immunological markers may indicate increased relapse risk, larger prospective studies are required to define independent predictors of MS conversion.

Newborn screening enables early detection and treatment of serious genetic conditions before symptom onset. Lysosomal diseases, a group of more than 70 rare inherited metabolic disorders, are increasingly considered for inclusion in NBS owing to advances in pathophysiological understanding and therapy development. Early, pre-symptomatic identification offers a critical window for intervention that can improve neurodevelopmental outcomes and quality of life. To evaluate the feasibility of high-throughput, multi-tiered newborn screening for 13 lysosomal diseases, in the LysoNeo pilot study, families of 106,609 newborns were approached between March 2021 and November 2024; 100,212 consented, and 100,000 newborns were successfully screened. Dried blood spots collected shortly after birth underwent a multi-tier screening process combining first-tier biochemical testing, repeat testing of abnormal samples, second-tier reassessment, multidisciplinary review and confirmatory biochemical and molecular investigations for recalled newborns. Among 106,609 families approached, consent is obtained for 100,212 (94.0%), and screening is successfully completed for 100,000 newborns. First-tier screening identifies 75 newborns with abnormal results (screen-positive rate: 0.075%). Following second-tier reassessment and multidisciplinary review, 14 newborns are recalled (recall rate: 0.014%). Eight newborns have concordant biochemical and molecular findings consistent with lysosomal disease (confirmed case rate: 0.008%; Predictive Positive Value among recalled: 57.1% [8/14]; Predictive Positive Value among first-tier positives: 10.6% [8/75]). Two newborns initiate disease-specific therapy and six remain under structured follow-up. LysoNeo demonstrates the feasibility of implementing expanded lysosomal diseases newborn screening within a regional healthcare system and provides real-world evidence on screening cascade dynamics and actionability-based governance to inform national policy. Newborn screening tests babies shortly after birth to find serious diseases before symptoms appear. Some rare genetic conditions, called lysosomal diseases, can cause severe health problems but may benefit from early treatment. We carried out a large pilot study in the Normandy region of France to assess whether screening for 13 of these diseases could be added safely and effectively to routine newborn screening. Between 2021 and 2024, more than 100,000 newborns were tested using a step-by-step process that combined blood tests and genetic analysis. Eight babies were confirmed to have a lysosomal disease. Two started treatments early, and six are being closely monitored. Our results show that large-scale screening for these rare diseases is possible and can identify affected children early, helping guide future decisions about expanding newborn screening programs.

This study aimed to (1) compare gait patterns between children with periventricular leukomalacia (PVL) and those with perinatal stroke and (2) assess between-subject gait variability within each group to quantify differences in the heterogeneity of gait patterns associated with distinct brain lesion types. A total of 43 children with cerebral palsy (CP) (32 PVL, 11 perinatal stroke) underwent three-dimensional gait analysis. Kinematic waveforms of the more affected leg and temporospatial gait parameters were compared between groups. Furthermore, between-subject gait variability in gait kinematics was evaluated. Differences in discrete kinematic parameters were assessed with Levene's tests. Dynamic time warping (DTW) quantified deviations from group mean trajectories, and principal component analysis (PCA) evaluated the number of components required to explain cumulative variance in gait patterns. Children with PVL and stroke did not differ significantly in temporospatial gait parameters or overall kinematic profiles, except for greater hip adduction during mid-stance in PVL. However, gait variability was consistently higher in the PVL group across analytical methods. PVL was associated with greater variability in knee flexion at initial contact (p&#x2009;=&#x2009;0.040) and a trend during swing (p&#x2009;=&#x2009;0.069). DTW distances were larger for PVL in sagittal knee kinematics (p&#x2009;=&#x2009;0.002), and PCA indicated that more components were needed to explain 90% of variance. Children with PVL exhibited greater between-subject gait variability than those with stroke, reflecting the diffuse nature of white matter injury. These findings highlight the importance of considering lesion type and gait variability when designing individualized rehabilitation strategies for children with CP.

Epilepsy is prevalent among &#x223c;50 million people worldwide. Updated information is lacking on the epidemiology and characteristics of epilepsy in Portugal. Therefore, a population-based study was conducted to estimate the prevalence and identify potential undiagnosed cases of epilepsy in children and adults in Portugal. This cross-sectional population-based study, conducted from May 2023 to July 2024, involved a nationwide door-to-door survey in Portugal (mainland and islands), screening 10,666 individuals. Trained interviewers visited selected households to recruit and interview participants, applying questionnaires to identify undiagnosed epilepsy cases and gather information about positive epilepsy diagnosis and management. Participants reporting positive screening were further evaluated by steering committee epileptologists for a potential epilepsy diagnosis. The study estimated a crude prevalence of epilepsy of 9.76 cases per 1000 people (95% CI 86,7-115,5) in Portugal. The average age of the prevalent cases was 44.22 years (&#xb1;21.99). Epilepsy was more common among females (55.8%), adults (&#x223c;82%), and residents of the North (45.5%), Center (26.6%), and Lisbon (15.3%) regions. Around 20% of the participants had not experienced seizures in the last 10 years. Also, &#x223c;44% of the participants were taking three or more antiseizure medications. The study indicates that Portugal's epilepsy prevalence is twice as high as reported in a 1998 study conducted in the north of Portugal and exceeds both global and European averages. Due to limitations such as the small number of confirmed cases and low physician contact rates, the representativeness of the study in certain regions or age groups should be interpreted with caution. Nevertheless, the high burden of epilepsy highlights the need for effective health programs and resource allocation.

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Glucose transporter type I (Glut1) deficiency syndrome (Glut1DS) is associated with paroxysmal exertion-induced dystonia (PED). Episodes are published as brief, lasting 20 to 30&#x2009;minutes. Increasingly, Glut1DS patients report prolonged PED of more than 1&#x2009;hour duration. In a cohort of 60 Glut1DS patients seen in our institution within a 4-year period, a total of 26/60 patients (43%) on ketogenic dietary therapy (KDT) experienced PED. In 18/26 patients (30%), episodes lasted less than 1&#x2009;hour as previously described. In 8/26 patients (13%), prolonged episodes lasted more than 1&#x2009;hour up to 1 day despite adequate dietary treatment. We conclude that PED is common in Glut1DS starting in late childhood despite adequate treatment with KDT. Prolonged PED in Glut1DS occurs in a subset of patients, also unresponsive to KDT, and represents a substantial burden to patients and families.

In France, 4866 cases of tuberculosis were reported in 2023, of which 5.3% involved children. The pediatric population is at higher risk of developing severe forms (miliary or meningeal tuberculosis). The BCG vaccine is effective in protecting young children against these severe forms. It is recommended for a targeted pediatric population, but vaccine coverage remains insufficient. Early prevention through identifying eligible newborns in maternity care could help improve vaccination coverage among high-risk populations. This study assessed caregivers' knowledge of BCG vaccination indications and circuits in two maternity wards in the city of Toulouse (France), using a questionnaire. A second evaluation was conducted after a training session and the distribution of practical tools, to measure their impact on caregivers' knowledge and involvement. Caregivers' knowledge of BCG vaccination indications was insufficient (2.2 &#xb1; 0.33 correct indications out of 6). The development and implementation of training and prevention tools for caregivers helped improve their understanding of vaccination indications (2.6 &#xb1; 0.14 correct indications), identification (22.6 vs 45%), and prevention (17.7 vs 30%) CONCLUSION: Targeted vaccination requires greater caregiver training efforts than generalized and/or mandatory vaccination to improve implementation. For BCG vaccination, such training should ideally be provided to maternity staff.

This prospective study investigated whole blood-based immune cell biomarkers for pulmonary tuberculosis (TB) immunoprofiling. Blood samples from 34 healthy controls and 51 tuberculosis patients were analyzed at three timepoints: Prior to therapy (T0), after 14 days of therapy (T1), and at the end of treatment (Te). Using multiparameter flow cytometry, 386 immune cell populations were analyzed. Predictive models were developed using two machine learning algorithms. A TB5LF change score, which was based on five cell populations, effectively distinguished tuberculosis patients from controls (AUC&#xa0;=&#xa0;0.89) and tuberculosis patients before and at the end of treatment (AUC&#xa0;=&#xa0;0.92). Similarly, the TB5Lasso score distinguished tuberculosis patients from controls (AUC&#xa0;=&#xa0;0.91) and tuberculosis patients before and at the end of treatment (AUC = 0.93) but was inversely correlated with disease severity (r=-0.43). Both scores included PD-L1+CD80- neutrophils and PD-L1+HLA-DR+ CD4+ lymphocytes, highlighting PD-L1-associated and Th1-related immune signatures as candidate biomarkers for TB immunoprofiling. These findings are exploratory and hypothesis-generating, providing a basis for future studies evaluating their potential utility in diagnostic and therapy-monitoring contexts.

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Acid sphingomyelinase deficiency (ASMD), historically known as Niemann-Pick disease, is a rare and potentially fatal lysosomal storage disease caused by pathogenic variants in the sphingomyelin phosphodiesterase 1 (SMPD1) gene, which encodes acid sphingomyelinase (ASM). Deficient ASM activity results in dysregulation of cellular membrane homeostasis and accumulation of sphingomyelin in multiple organs. ASMD spans a broad clinical spectrum, with symptoms varying at presentation depending on age at onset and degree and type of organ/systemic involvement. To describe the diagnostic experience and clinical manifestations of ASMD in Argentina, a national retrospective case series was conducted across seven centers in patients diagnosed between 1988 and 2022. Diagnosis was confirmed by reduced ASM activity, with SMPD1 sequencing performed when possible. Nineteen patients (8 females/11 males; 0-76&#x2009;years) were identified: Type A (4, 21%), Type B (12, 63%), Type A/B (2, 11%), and one unknown. Average age at symptom onset was 3.9&#x2009;years, and average age at diagnosis was 11.4&#x2009;years, corresponding to a diagnostic delay of 7.5&#x2009;years. All patients presented with hepatosplenomegaly. Anemia (79%), pulmonary involvement (79%), thrombocytopenia (79%), and osteopenia (56%) were also reported in a majority of patients. Two patients were initially misdiagnosed with Gaucher disease. This series highlights the variety of clinical presentations and substantial diagnostic delays associated with ASMD in Argentina. Increasing awareness across specialties is essential to improve disease recognition, reduce time to diagnosis, and prevent misdiagnosis.

Intracerebral gene therapy is effective for amino acid decarboxylase (AADC) deficiency, but relationships between anatomical putaminal coverage, metabolic dynamics, and clinical recovery remain poorly understood. Assess safety, long-term efficacy, and clinical-radiological correlations in a genetically diverse European cohort of AADC deficiency. Six patients received bilateral intraputaminal rAAV2-hAADC infusion. Motor (GMFM-88), functional (CP-CHILD, Vineland-II), oculogyric crises (OGC), and dyskinesia outcomes were evaluated alongside magnetic resonance imaging (MRI) volumetric coverage and longitudinal 18F-fluorodopa (18F-DOPA) positron emission tomography (PET) parameters. All patients achieved genotype-independent motor improvements and OGC reduction, with no serious adverse events. Clinical recovery did not correlate with the putaminal coverage volume, indicating a biological threshold effect. Transient dyskinesias coincided with an early 18F-DOPA uptake peak (1-3&#x2009;months post-operative), followed by clinical resolution and sustained activity, reflecting homeostatic synaptic plasticity. Eladocagene exuparvovec offers durable clinical benefits across diverse genotypes. Therapeutic efficacy and the subsequent neuroplasticity sequence seem to depend on reaching a critical threshold of dopamine production rather than on exhaustive anatomical coverage of the putamen. &#xa9; 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

For youth living with neurodisabilities and rare conditions, transitioning from pediatric to adult care results in significant loss of services and supports. This article examines transition-related health systems, policies and provider roles in the context of Duchenne muscular dystrophy (DMD). DMD is a multi-systemic X-linked disorder mainly characterized by progressive muscle degeneration, with about 30% of patients presenting with neurodevelopmental comorbidities. Due to advances in respiratory and cardiac care, life expectancy has increased significantly, creating a new population of adults living with DMD. This demographic shift has exposed critical gaps in the transition from pediatric to adult health care. To date, there is no systematic review covering existing transition policies and programs. This article utilizes integrated care and continuity of care frameworks to examine transition-related health systems, policies, and provider roles. We conducted a PRISMA-compliant systematic review searching OVID Medline, Embase, PsycINFO, CINAHL, Web of Science, and SCOPUS from January 1, 2000, to August 31, 2025. Studies were included if they reported on health systems, programs, policies or health care providers' roles in DMD. For synthesizing evidence, we utilized Popay's Narrative Synthesis framework to analyze health systems, policies, and provider roles across included studies, allowing for an aggregation of a body of heterogenous data (quantitative, qualitative and mixed-methods). This methodological approach ensured that the review moved beyond a simple aggregation of findings to generate new insights into the structural gaps. 42 studies met the inclusion criteria. The programs described in these studies varied from residential life-skills training to respiratory-focused transition protocols. A significant disconnect was identified between international care guidelines and implementation; most initiatives are project-based rather than policy-driven. While neurology is central in pediatric care, respiratory and sleep medicine often become the de facto "medical home" for adults. Crucially, support for patients with neurodiverse development was only discussed in 4 of the 42 studies. This review underlines a lack of comprehensive care models for DMD transition, specifically within the high-resource settings that dominate the literature. Future policies must bridge the gap between project-based funding and sustainable health systems, specifically addressing neurodiversity and caregiver burden.

We report a 16-year-old girl with progressive ataxia, gaze palsy, and psychotic symptoms suggestive of Niemann-Pick disease type C (NPC). Despite strong clinical and biochemical evidence, including elevated N-palmitoyl-O-phosphocholine-serine (PPCS or lysosphingomyelin-509 [lyso-SM-509]), conventional genetic testing was inconclusive. RNA sequencing of fibroblasts revealed a homozygous NPC1 intronic variant (c.3246-25A&#x2009;>&#x2009;G) causing aberrant splicing. Miglustat was initiated, leading to clinical stabilization. A systematic literature review identified 12 patients with intronic splice-altering variants located outside the canonical splice donor and acceptor regions, including variants situated more than 20&#x2009;bp from exon-intron boundaries, predominantly affecting NPC1. Most patients presented with juvenile- or adult-onset disease and showed heterogeneous biomarker profiles. This case highlights the diagnostic utility of RNA sequencing in unsolved NPC cases and emphasizes its role in uncovering cryptic pathogenic variants, enabling timely diagnosis and treatment. Intronic variants should be considered in genetically elusive but clinically compatible NPC presentations.

Up to 30% of adults with peripheral facial palsy (FP) develop synkinesis, but it's incidence in children remains unclear due to limited long-term data. Children (<18 years) treated for acute peripheral FP at Jena University Hospital between 2009 and 2021 were screened in this cross-sectional study. Bell's palsy and infection-associated FP (e.g., Lyme disease, Zoster) were included, while secondary causes such as tumors, trauma, CNS disorders, and conditions like Guillain-Barr&#xe9; syndrome or Chiari malformation were excluded. Video follow-ups collected clinicodemographic information and PROMs including Facial Clinimetric Evaluation Scale (FaCE), Facial Disability Index (FDI), and Synkinesis Assessment Questionnaire (SAQ). Facial movements were video-recorded and assessed using Sunnybrook and eFACE. Of 85 eligible patients, 26 participated (46% female; response rate 30.6%). Mean age at onset was 8.5 years (range: 0.2-16); 54% had idiopathic FP (IFP) and 46% Lyme-associated FP (LFP). Median follow-up was 7.56 years (range: 2.5-13). All LFP participants and 11 out of 14 IFP participants achieved complete or near-complete recovery (eFACE and Sunnybrook scores 90-100). Four participants (28.6%), exclusively from the IFP group, developed synkinesis, three with functional impairments in PROMs and video-based assessment. Seven participants (five (35.7%) from the IFP group and two (16.7%) from the LFP group) reported that they still experience mental health-related effects of FP today. The data indicate that a relevant proportion (around 21.4%) of children with Bell's palsy develop moderate to severe synkinesis. Long-term follow-up and further research on corticosteroids use in pediatric FP are warranted.

To characterise age-related changes in sleep macroarchitecture, consolidation and fragmentation across childhood and adolescence in a large real-world paediatric clinical polysomnography cohort, and to examine their relationship with respiratory disturbance severity. We performed a retrospective observational analysis of 419 polysomnographies from children aged 1-18&#xa0;years at a tertiary sleep unit between January 2023 and December 2024. Participants were categorised as toddlers, pre-schoolers, school-aged children and adolescents. Sleep macroarchitecture, consolidation and fragmentation parameters were scored according to paediatric American Academy of Sleep Medicine criteria. Multivariate general linear models assessed age-group differences, with additional adjustment for apnoea-hypopnoea index and Bonferroni post-hoc testing. Total sleep time decreased with age, while sleep onset and rapid eye movement sleep latencies increased during adolescence. Sleep architecture showed a developmental shift, mainly characterised by increasing Stage N2 and decreasing rapid eye movement sleep proportions, with less robust changes in Stage N3. Fragmentation indices, including arousal index, were higher in adolescents. After adjustment for apnoea-hypopnoea index, age group remained an independent predictor of macroarchitecture, consolidation and fragmentation, whereas respiratory severity was mainly associated with micro-fragmentation indices. Sleep macroarchitecture continues to mature throughout childhood and adolescence, with adolescents frequently exhibiting adult-like sleep patterns largely independent of respiratory disturbance severity. Age-related changes in sleep macroarchitecture and fragmentation provide physiological context for interpreting paediatric polysomnography, particularly near the transition between paediatric and adult scoring frameworks.

Effective clinical communication is a core component of patient-centered care. Immersive learning technologies, including virtual patients, virtual reality, and augmented reality, are increasingly used to train clinical communication skills in undergraduate health professions education. However, the existing evidence is fragmented and methodologically heterogeneous. This umbrella review synthesizes review-level evidence on immersive technologies and virtual patients for developing clinical communication skills in undergraduate health professions education and explores barriers to curricular integration and key research gaps. An umbrella review of systematic reviews (with or without meta-analysis) was conducted following PRISMA guidelines. Searches were performed in PubMed, ScienceDirect, CINAHL, and Cochrane Library. Eligible reviews examined immersive technologies (e.g., VR, AR, MR, XR, virtual patients) targeting clinical communication skills in undergraduate learners. Methodological quality was assessed using AMSTAR-2. No pooled meta-analysis was feasible because of substantial heterogeneity in interventions, comparison conditions, and outcome measures. Nine systematic reviews were included. All were rated as critically low in methodological quality, which limits confidence in the conclusions that can be drawn. Across reviews, immersive technologies were reported as potentially beneficial for short-term communication performance, learner engagement, and perceived confidence, particularly in comparison with no intervention or some traditional teaching formats. However, evidence regarding long-term retention, empathy development, non-verbal communication, and transfer to clinical practice remained inconsistent. Substantial heterogeneity in intervention design, outcome measures, and feedback structures limited comparability across reviews.