Mucopolysaccharidosis type IIIC (MPS IIIC) is a rare lysosomal storage disorder caused by biallelic pathogenic variants in the HGSNAT gene, encoding heparan-α-glucosaminide N-acetyltransferase. Deficient enzymatic activity leads to heparan sulfate accumulation, resulting in progressive central nervous system involvement and multisystem disease. Clinical features typically include developmental delay, intellectual disability, behavioral disturbances, coarse facial features, hypertrichosis, and hearing loss. This report describes the oldest documented siblings with MPS IIIC: a male diagnosed at 46 years (currently 50 years) and his sister diagnosed at 38 years (currently 42 years). Both presented with bilateral sensorineural hearing loss, retinitis pigmentosa, intellectual disability, mildly coarse facial features, and hypertrichosis. Molecular analysis identified two novel HGSNAT variants: c.1205T>C; p.(Leu402Pro) and c.1565C>A; p.(Thr522Lys). Functional studies demonstrated markedly reduced heparan-α-glucosaminide N-acetyltransferase activity and elevated urinary heparan sulfate excretion, providing biochemical evidence supporting variant pathogenicity and confirming the diagnosis. These cases expand both the phenotypic and genotypic spectrum of MPS IIIC and underscore the importance of considering this disorder in adults with multisystem involvement. Functional characterization proved essential for establishing a definitive diagnosis when molecular findings alone were inconclusive.
This research outlines the development and validation of the Alimetry® Gut-Brain Wellbeing Survey-Youth Version (AGBW-Y), a novel tool for assessing mental health in young people with chronic gastroduodenal symptoms aged 12–17 years. In Phase 1, global feedback was gathered from 19 pediatric clinicians in the gastroenterology field and 33 young people over multiple rounds to make the adult AGBW Survey more age-appropriate for young people. In Phase 2, rigorous psychometric testing was conducted in a sample of 128 patients aged 12–17 years with chronic gastroduodenal symptoms, using an anonymous survey. Based on the feedback from Phase 1, an interdisciplinary team of experts improved the survey’s language and usability for young people to enhance the scale’s clarity, acceptability, and face and content validity. The final AGBW-Y comprises a patient preface, 10 closed-ended questions, and an open-ended question. It assesses general mental health, alongside subscales of depression, stress, and anxiety. Phase 2 demonstrated excellent psychometric properties of the scale, including high internal consistency reliability (α = 0.91 for the total scale; α = 0.75–0.85 for subscales) and strong convergent, divergent, and concurrent validity with large effect sizes. The AGBW-Y is a brief, reliable, and valid tool to assess mental health in young people aged 12–17 years with chronic gastroduodenal symptoms. This novel scale was developed through rigorous co-design with clinicians and young people, ensuring it is contextually relevant and clinically impactful. The AGBW-Y complements existing physiological assessments, enabling evaluations that can guide psychological referrals, support multidisciplinary care, and evaluate treatment outcomes.
Background:Pediatric low-grade gliomas (pLGGs) are the most common childhood central nervous system (CNS) tumors. Targeted therapies are effective treatments in patients with pLGGs harboring mutations in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK) signaling pathway. Understanding the toxicity profile and tolerability of emerging MAPK inhibitors (MAPKi) and how adverse events (AEs) can be managed to avoid treatment discontinuation, interruption, or dose reduction is important for optimizing clinical benefit. Methods:A modified Delphi consensus initiative was conducted to provide recommendations on the monitoring and management of AEs that occur with MAPKi in patients with pLGG. A 9-member steering committee was convened to develop statements based on the findings of a comprehensive literature review of AEs reported with the use of MAPKi in pediatric cancers. Consensus on statements was determined via online surveys completed by a large, global panel of experts in pLGG. Results:Of the 129 statements drafted, consensus (≥75% agreement) among 82 global experts in pLGG was reached for 50 statements, mostly pertaining to the general management of AEs occurring with MAPKi and the management of cutaneous AEs. Consensus statements include guidance on skin care and specific cutaneous conditions. Many AEs were rare with limited evidence or experience to achieve consensus recommendations. Conclusions:The consensus statements developed provide guidance and recommendations for the management of common AEs in patients with pLGG treated with MAPKi. Sharing this knowledge may lead to patients with pLGG achieving optimal benefit from MAPKi while minimizing and effectively managing AEs.
Improvements in organization, time management, and planning (OTMP) skills have downstream effects on student academic performance. Brief, practical assessment tools are needed to identify students needing OTMP intervention and monitor response to intervention. The purpose of this study was to develop and validate brief rating scales of OTMP skills, derived from the Children’s Organizational Skills Scale parent and teacher versions (COSS-P, COSS-T), for screening and progress monitoring. Three samples were used: (1) general and clinical sample (n for caregivers = 1155; n for teachers = 1139; Abikoff Gallagher, 2009); (2) sample from the randomized controlled trial (RCT) evaluating Organizational Skills Training-Tier 2 (OST-T2; n = 185; Nissley-Tsiopinis et al., 2024); (3) sample from the RCT evaluating Homework, Organization, and Planning Skills (HOPS; n = 163; Langberg et al., 2018). Based on indices of discrimination and item effect sizes, we identified 10 items from the COSS-P/T representing multiple components of OTMP interventions, in addition to one item assessing OTMP interference with performance. Confirmatory factor analyses demonstrated strong fit to a bifactor model. Only the general factor demonstrated acceptable reliability. The total score demonstrated convergent validity with measures of school and executive functioning and was excellent in differentiating children with and without substantial, impairing OTMP deficits (Area Under Curve [AUC] = .947 for COSS-P, .982 for COSS-T). Treatment sensitivity for the screeners and three, five-item formative behavior assessment measures, computed as effect sizes (Cohen’s d) based on response to OST-T2 and HOPS, all exceeded −1.20. The brief tools developed in this study have substantial utility for screening and progress monitoring.
Persons with disorders of consciousness (DoC) occupy an ethically charged space in modern medicine and biomedical research. Their decisional capacity is characteristically absent or limited or unpredictably fluctuates, requiring clinicians and investigators to rely on surrogates. Although there is general guidance for informed consent (IC) for research studies, there is no specific guidance for research involving persons with DoC. There are inconsistencies in IC forms for these studies related to explanation of a DoC, evaluation of capacity, description of risks/benefits, and sharing investigational results. This is problematic for persons with DoC, their surrogates, researchers, and institutional review boards (IRBs)/research ethics boards (REBs). To address these issues, the Curing Coma Campaign (CCC) Ethics Workgroup developed the Common Consent Elements for Research Involving Persons with Disorders of Consciousness (CCE-DoC). This practical framework aims to clarify and standardize consent processes in this complex and ethically sensitive research area. Through this structured, adaptable approach, CCE-DoC may have the potential to enhance participant protections, strengthen trust, help families and decision-makers understand studies, reduce duplicative efforts across research groups, and guide investigators and IRBs/REBs in navigating the complex ethical terrain of consent in DoC research. In so doing, CCE-DoC seeks to extend respect for autonomy and trust and promote responsible research urgently needed to advance paradigms of diagnosis, prognosis, and treatment for individuals with disorders of consciousness. The framework offers example language to encourage standardization, while allowing teams flexibility to customize to local needs.
