Expedited Exome Reanalysis Following Deep Phenotyping and Muscle Biopsy in Suspected Mitochondrial Disorder.

Background: Exome sequencing (ES) is a useful tool in diagnosing suspected mitochondrial disease but can miss pathogenic variants for several reasons. Additional testing, such as muscle biopsy or biochemical testing, can be helpful in exome-negative cases.

Methods: We report a patient who presented with repeated episodes of lactic acidosis and failure to thrive.

Disease characteristics, effectiveness, and safety of vestronidase alfa for the treatment of patients with mucopolysaccharidosis VII in a novel, longitudinal, multicenter disease monitoring program.

Background: Mucopolysaccharidosis VII (MPS VII) is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by reduced activity of β-glucuronidase (GUS) enzyme. Vestronidase alfa (recombinant human GUS) intravenous enzyme replacement therapy is an approved treatment for patients with MPS VII.

Methods: This disease monitoring program (DMP) is an ongoing, multicenter observational study collecting standardized real-world data from patients with MPS VII (N ≈ 50 planned) treated with vestronidase alfa or any other management approach.

variants in the non-coding spliceosomal snRNA gene are a frequent cause of syndromic neurodevelopmental disorders.

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes. Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA as a novel syndromic NDD gene.

An updated management approach of Pompe disease patients with high-sustained anti-rhGAA IgG antibody titers: experience with bortezomib-based immunomodulation.

Introduction: High sustained anti-rhGAA antibody titers (HSAT; ≥12,800) are directly linked to reduced efficacy of enzyme replacement therapy (ERT) and subsequent clinical deterioration in infantile-onset Pompe disease (IOPD). We have previously demonstrated the safety and effectiveness of a bortezomib-based immune-tolerance induction (ITI) regimen (bortezomib, rituximab, methotrexate, and IVIG) in eliminating HSAT.

Methods: Here, we describe two IOPD cases (patients 6 and 8) who developed HSAT at 8 and 10 weeks on ERT despite transient low-dose methotrexate ITI administration in the ERT-naïve setting and were treated with a bortezomib-based ITI regimen, and we compare their courses to a series of six historical patients (patients 1-5, and 7) with a similar presentation who exemplify our evolving approach to treatment.

Assessing the feasibility of an intervention for adolescents and parents transitioning out of paediatric eating disorder services: A mixed methods study.

Objective: To assess the feasibility of a new intervention designed to support adolescents and parents in the transition from paediatric eating disorder (ED) treatment to adult mental health services.

Method: Pre-transition adolescents with EDs, and their parents, were invited to complete up to five transition intervention components over 3 months. A mixed methods design was used to assess intervention feasibility, comprised of acceptability and preliminary effectiveness.

Uniparental disomy of multiple chromosomes in two cases with a complex phenotype.

Uniparental disomy (UPD) is the inheritance of both chromosomal homologs from one parent. Depending on the chromosome involved and the parental origin, UPD may result in phenotypic abnormalities due to aberrant methylation patterns or unmasking recessive conditions in isodisomic regions. UPD primarily originates from somatic rescue of a single meiotically-derived aneuploidy, most commonly a trisomy.

Opportunities and challenges in capturing severe vaping-related injuries among Canadian children and youth.

Although the long-term harms associated with vaping remain largely unknown, there have been numerous accounts of acute vaping-related injuries in the paediatric population. The study of vaping-related injuries is an important yet challenging undertaking, complicated by a lack of appropriate reporting mechanisms and the absence of consensus on definitions and diagnostic codes. We discuss the results of a 12-month national cross-sectional study from the Canadian Paediatric Surveillance Program conducted in 2021-2022 and situate these results within the broader context of other Canadian surveillance and reporting mechanisms.

De novo variants in H3-3A and H3-3B are associated with neurodevelopmental delay, dysmorphic features, and structural brain abnormalities.

The histone H3 variant H3.3, encoded by two genes H3-3A and H3-3B, can replace canonical isoforms H3.1 and H3.

Counselling adolescents and parents about cannabis: A primer for health professionals.

While cannabis use among adolescents is frequent in Canada, youth do recognize the potential harms, and increasingly expect knowledgeable health care providers to discuss substance use in everyday practice. This practice point provides sound, evidence-based tools to help health professionals address nonmedical (recreational) cannabis use and its related risks. After highlighting how to make the clinical setting a safe space for youth to talk about psychoactive substances, specific strategies for approaching cannabis use in effective, developmentally appropriate ways are described.

Impending Transition From Pediatric to Adult Health Services: A Qualitative Study of the Experiences of Adolescents With Eating Disorders and Their Caregivers.

There is a dearth of research that identifies pediatric to adult health care transition practices that yield positive outcomes for young people with eating disorders (EDs). Further, adolescent and caregiver perspectives are poorly understood and underrepresented in the literature. The purpose of this study, focused on the impending transition from pediatric to adult health services, was twofold: (a) to identify adolescent and caregiver perspectives of barriers and facilitators of a successful transition for adolescents with EDs; and (b) to understand adolescent and caregiver suggestions of interventions for a successful transition.

Multimodal therapy for rigid, persistent avoidant/restrictive food intake disorder (ARFID) since infancy: A case report.

Avoidant/restrictive food intake disorder (ARFID) is a feeding and eating disorder that results in nutritional inadequacies, weight loss, and/or dependence on enteral feeds, and for which three clinical subtypes have been described. We present a unique case of an 11-year-old boy with rigid ARFID since infancy and features of all three ARFID subtypes. The patient presented with a life-long history of sensory aversion, limited intake and phobia of vomiting resulting in restriction to a single food item (yogurt) for more than 5 years.

Mucopolysaccharidosis type I newborn screening: Importance of second tier testing for ethnically diverse populations.

Mucopolysaccharidosis type I (MPS I)/Hurler syndrome newborn screening was added to the recommended uniform screening panel (RUSP) in 2016. As states have added screening for MPS I, programs have reported increased rates of false positives. Reasons for false positive screens include carrier status, true false positive, late-onset/attenuated forms, and in about half of cases, pseudodeficiency alleles.

ASAH1 pathogenic variants associated with acid ceramidase deficiency: Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy.

Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy are a spectrum of rare lysosomal storage disorders characterized by acid ceramidase deficiency (ACD), resulting from pathogenic variants in N-acylsphingosine amidohydrolase 1 (ASAH1). Other than simple listings provided in literature reviews, a curated, comprehensive list of ASAH1 mutations associated with ACD clinical phenotypes has not yet been published. This publication includes mutations in ASAH1 collected through the Observational and Cross-Sectional Cohort Study of the Natural History and Phenotypic Spectrum of Farber Disease (NHS), ClinicalTrials.

Recent Advances in Systems and Network Medicine: Meeting Report from the First International Conference in Systems and Network Medicine.

The gathered together 200 global thought leaders, scientists, clinicians, academicians, industry and government experts, medical and graduate students, postdoctoral scholars and policymakers. Held at Georgetown University Conference Center in Washington D.C.

Human knockout cerebral organoids: A model system for testing AAV9-mediated gene therapy for reducing GM1 ganglioside storage in GM1 gangliosidosis.

GM1 gangliosidosis is an autosomal recessive neurodegenerative disorder caused by the deficiency of lysosomal β-galactosidase (β-gal) and resulting in accumulation of GM1 ganglioside. The disease spectrum ranges from infantile to late onset and is uniformly fatal, with no effective therapy currently available. Although animal models have been useful for understanding disease pathogenesis and exploring therapeutic targets, no relevant human central nervous system (CNS) model system has been available to study its early pathogenic events or test therapies.

How can transition to adult care be best orchestrated for adolescents with epilepsy?

Objective evidence is limited for the value of transition programs for youth with chronic illness moving from pediatric to adult care; however, such programs intuitively "make sense". We describe the strengths and weaknesses of a variety of transition programs from around the world for adolescents with epilepsy. Consequences of poorly organized transition beyond suboptimal seizure control may include an increased risk of sudden unexpected death in epilepsy (SUDEP), poor psychological and social outcome, and inadequate management of comorbidities.

Cannabis and Canada's children and youth.

Cannabis is the most common illicit drug used worldwide and it is used frequently by Canadian teenagers. Cannabis use during adolescence can cause functional and structural changes to the developing brain, leading to damage. Marijuana use in this age group is strongly linked to: cannabis dependence and other substance use disorders; the initiation and maintenance of tobacco smoking; an increased presence of mental illness, including depression, anxiety and psychosis; impaired neurological development and cognitive decline; and diminished school performance and lifetime achievement.

Fear of Vomiting and Low Body Weight in Two Pediatric Patients: Diagnostic Challenges.

Fear of vomiting can be a symptom associated with several disorders, including Eating Disorders (ED), Specific Phobia (Emetophobia), Avoidant Restrictive Food Intake Disorder (ARFID) and Obsessive Compulsive Disorder (OCD), making proper diagnosis challenging. At this time the literature exploring this symptom is limited, and to our knowledge very few cases have been described in the child and adolescent population. We report here the cases of one child and one adolescent presenting with significant weight loss, food restriction and fear of vomiting.