Lysosomal storage diseases (LSDs) are a heterogeneous group of rare multisystem genetic disorders occurring mostly in infancy and childhood, characterized by a gradual accumulation of non-degraded substrates inside the lysosome. Although the cellular pathogenesis of LSDs is complex and still not fully understood, the approval of disease-specific therapies and the rapid emergence of novel diagnostic methods led to the implementation of extensive national newborn screening (NBS) programs in several countries. In the near future, this will help the development of standardized workflows aimed to more timely diagnose these conditions. Hereby, we report an overview of LSD diagnostic process and treatment strategies, provide an update on the worldwide NBS programs, and discuss the opportunities and challenges arising from genomics applications in screening, diagnosis, and research.

Megalencephaly capillary malformation polymicrogyria (MCAP) syndrome is characterized by the sporadic occurrence of congenital and progressive megalencephaly, brain malformations including polymicrogyria, pre- and postnatal overgrowth with body asymmetry, cutaneous vascular malformations (including capillary malformation and cutis marmorata), digital anomalies connective tissue dysplasia (including skin and joint laxity), and developmental delay. In the past 10 years, the specific cause of the disease has been found in gain-of-function mutations of PIK3CA gene, mostly somatic/postzygotic but in rare cases also de novo germline. Such gene encodes for PI3K, a critical member of the PI3K-AKT-mTOR pathway: genetic changes lead to an over-activation of this signaling system, with increased vascular, limb, and brain cell development, progression, and survival. Interestingly, mutations in the same gene can cause other clinically heterogeneous syndromes, including CLOVE syndrome, macrodactyly, focal adipose overgrowth, epidermal nevi, facial infiltrating lipomatosis: all these syndromes (even if heterogeneous) are now considered a unique spectrum, known as PIK3CA-related overgrowth syndrome. On the contrary, a disease strictly similar to MCAP, characterized by megalencephaly, polymicrogyria, polydactyly, and hydrocephalus has been found to be caused by mutations in two other PI3K-AKT-mTOR-releted genes, AKT3 and PIK3R2, and for this reason is not included in the upper mentioned group of syndromes. With the exception of neurosurgery strategies for hydrocephalus and posterior fossa overcrowding, therapeutic options are nowadays limited, even if gene-targeted treatment protocols have been proposed and protocols with such agents (i.e., Arq092) are currently ongoing in small groups of patients with promising results.

Background: Motor Imagery (MI) is a cognitive process consisting in mental simulation of body movements without executing physical actions: its clinical use has been investigated prevalently in adults with neurological disorders.Objectives: Review of the best-available evidence on the use and efficacy of MI interventions for neurorehabilitation purposes in common and rare childhood neurological disorders.Methods: systematic literature search conducted according to PRISMA by using the Scopus, PsycArticles, Cinahl, PUBMED, Web of Science (Clarivate), EMBASE, PsychINFO, and COCHRANE databases, with levels of evidence scored by OCEBM and PEDro Scales.Results: Twenty-two original studies were retrieved and included for the analysis; MI was the unique or complementary rehabilitative treatment in 476 individuals (aged 5 to 18 years) with 10 different neurological conditions including, cerebral palsies, stroke, coordination disorders, intellectual disabilities, brain and/or spinal cord injuries, autism, pain syndromes, and hyperactivity. The sample size ranged from single case reports to cohorts and control groups. Treatment lasted 2 days to 6 months with 1 to 24 sessions. MI tasks were conventional, graded or ad-hoc. MI measurement tools included movement assessment batteries, mental chronometry tests, scales, and questionnaires, EEG, and EMG. Overall, the use of MI was stated as effective in 19/22, and uncertain in the remnant studies.Conclusion: MI could be a reliable supportive/add-on (home-based) rehabilitative tool for pediatric neurorehabilitation; its clinical use, in children, is highly dependent on the complexity of MI mechanisms, which are related to the underlying neurodevelopmental disorder.

Lysosomal storage diseases (LSDs) are a heterogeneous group of approximately 70 monogenic metabolic disorders whose diagnosis represents an arduous challenge for clinicians due to their variability in phenotype penetrance, clinical manifestations, and high allelic heterogeneity. In recent years, the approval of disease-specific therapies and the rapid emergence of novel rapid diagnostic methods has opened, for a set of selected LSDs, the possibility for inclusion in extensive national newborn screening (NBS) programs. Herein, we evaluated the clinical utility and diagnostic validity of a targeted next-generation sequencing (tNGS) panel (called NBS_LSDs), designed ad hoc to scan the coding regions of six genes (GBA, GAA, SMPD1, IDUA1, GLA, GALC) relevant for a group of LSDs candidate for inclusion in national NBS programs (MPSI, Pompe, Fabry, Krabbe, Niemann Pick A-B and Gaucher diseases). A standard group of 15 samples with previously known genetic mutations was used to test and validate the entire flowchart. Analytical accuracy, sensitivity, and specificity, as well as turnaround time and costs, were assessed. Results showed that the Ion AmpliSeq and Ion Chef System-based high-throughput NBS_LSDs tNGS panel is a fast, accurate, and cost-effective process. The introduction of this technology into routine NBS procedures as a second-tier test along with primary biochemical assays will allow facilitating the identification and management of selected LSDs and reducing diagnostic delay.

In Sicily (Italy), respiratory syncytial virus (RSV), rhinovirus (HRV), and influenza virus triggered epidemics among children, resulting in an increase in acute respiratory tract infections (ARTIs). Our objective was to capture the epidemiology of respiratory infections in children, determining which pathogens were associated with respiratory infections following the lockdown and whether there were changes in the epidemiological landscape during the post-SARS-CoV-2 pandemic era. Materials and Methods: We analyzed multiplex respiratory viral PCR data (BioFire^® FilmArray^® Respiratory Panel 2.1 Plus) from 204 children presenting with respiratory symptoms and/or fever to our Unit of Pediatrics and Pediatric Emergency. Results: Viruses were predominantly responsible for ARTIs (99%), with RSV emerging as the most common agent involved in respiratory infections, followed by human rhinovirus/enterovirus and influenza A. RSV and rhinovirus were also the primary agents in coinfections. RSV predominated during winter months, while HRV/EV exhibited greater prevalence than RSV during the fall. Some viruses spread exclusively in coinfections (human coronavirus NL63, adenovirus, metapneumovirus, and parainfluenza viruses 1–3), while others primarily caused mono-infections (influenza A and B). SARS-CoV-2 was detected equally in both mono-infections (41%) and coinfections (59%). Conclusions: Our analysis underlines the predominance of RSV and the importance of implementing preventive strategies for RSV.

Background. It has been shown in the very recent literature that human walking generates rhythmic motor patterns with hidden time harmonic structures that are represented (at the subject’s comfortable speed) by the occurrence of the golden ratio as the the ratio of the durations of specific walking gait subphases. Such harmonic proportions may be affected—partially or even totally destroyed—by several neurological and/or systemic disorders, thus drastically reducing the smooth, graceful, and melodic flow of movements and altering gait self-similarities. Aim. In this paper we aim at, preliminarily, showing the reliability of a technologically assisted methodology—performed with an easy to use wearable motion capture system—for the evaluation of motion abilities in Ataxia-Telangiectasia (AT), a rare infantile onset neurodegenerative disorder, whose typical neurological manifestations include progressive gait unbalance and the disturbance of motor coordination. Methods. Such an experimental methodology relies, for the first time, on the most recent accurate and objective outcome measures of gait recursivity and harmonicity and symmetry and double support subphase consistency, applied to three AT patients with different ranges of AT severity. Results. The quantification of the level of the distortions of harmonic temporal proportions is shown to include the qualitative evaluations of the three AT patients provided by clinicians. Conclusions. Easy to use wearable motion capture systems might be used to evaluate AT motion abilities through recursivity and harmonicity and symmetry (quantitative) outcome measures.