Background: Telemedicine represents a growing opportunity to improve access to personalized care for patients with rare diseases, addressing the challenges of specialized healthcare that is often limited by geographical barriers. The aim of this narrative review is to explore how telemedicine can facilitate tailored nutritional interventions for rare diseases, focusing on inherited metabolic diseases, rare neurological disorders, such as leukodystrophies, and neuromuscular disorders, including spinal muscular atrophies. Methods: This narrative review is based on a systematic search of the published literature over the past 20 years, and includes systematic reviews, meta-analysis, retrospective studies, and original articles. References were selected through searches in databases such as PubMed and Scopus, applying predefined inclusion and exclusion criteria. Among the inclusion criteria, studies focusing on pediatric patients aged 0 to 18 years, diagnosed with rare neurological diseases or inherited metabolic disorders, and using telemedicine in addition to in-person visits at their reference center were considered. Among the exclusion criteria, studies involving patients with other pathologies or comorbidities and those involving patients older than 18 years were excluded. Results: A total of 66 documents were analyzed to examine the challenges and specific needs of patients with rare diseases, highlighting the advantages and limitations of telemedicine compared to traditional care. The use of telemedicine has revolutionized the medical approach, facilitating integrated care by multidisciplinary teams. Conclusions: Telemedicine still faces several technical, organizational, and security challenges, as well as disparities in access across different geographical areas. Emerging technologies such as artificial intelligence could positively transform the monitoring and management of patients with rare diseases. Telemedicine has great potential ahead of it in the development of increasingly personalized and effective care, in fact, emerging technologies are important to provide remote care, especially for patients with rare diseases.

Background: Sleep disorders have been poorly described in congenital (CDM) and childhood (ChDM) myotonic dystrophy despite being highly burdensome. The aims of this study were to explore sleep disorders in a cohort of Italian CDM and ChDM and to assess their association with motor and respiratory function and disease-specific cognitive and behavioral assessments. Methods: This was an observational multicenter study. Reported sleep quality was assessed using the Pediatric Daytime Sleepiness Scale (PDSS) and Pediatric Sleep Questionnaire (PSQ). Sleep quality was correlated to motor function (6 min walk test, 6MWT and grip strength; pulmonary function (predicted Forced Vital Capacity%, FVC% pred.); executive function assessed by BRIEF-2; autism traits assessed by Autism Spectrum Screening Questionnaire (ASSQ) and Repetitive Behavior Scale-revised (RBS-R); Quality of life (PedsQL) and disease burden (Congenital Childhood Myotonic Dystrophy Health Index, CCMDHI). Results: Forty-six patients were included, 33 CDM and 13 ChDM, at a median age of 10.4 and 15.1 years. Daytime sleepiness and disrupted sleep were reported by 30% children, in both subgroups of CDM and ChDM. Daytime sleepiness correlated with autism traits in CDM (p < 0.05). Disrupted sleep correlated with poorer executive function (p = 0.04) and higher disease burden (p = 0.03). Conclusions: Sleep issues are a feature of both CDM and ChDM. They correlate with behavioral issues and impact on disease burden.

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder, caused by mutations in the ABCD1 gene. Early diagnosis is critical to manage adrenal insufficiency and cerebral forms of the disease. Since 2021, a pilot newborn screening (NBS) program for X-ALD has been launched in Lombardy, Italy. From September 2021 to June 2025, 138,116 newborns (≥37 weeks’ gestational age) were screened for elevated C26:0-lysophosphatidylcholine (C26:0-LPC) levels using a two-tier algorithm. Genetic testing was performed in non-negative cases. Males found to be ABCD1 variant carriers were enrolled in multidisciplinary follow-up, including neurological, endocrinological, and nutritional assessments. Eleven individuals (six males, five females) carried pathogenic or likely pathogenic ABCD1 variants. Three males were diagnosed with adrenal insufficiency and started hydrocortisone therapy between 1 and 2 years of age. Growth parameters were within normal range overall, but two children showed signs of stunting associated with poor dietary compliance. Additionally, three patients were diagnosed with Zellweger spectrum disorders (ZSDs). No patients affected with Aicardi-Goutières Syndrome were identified. Newborn screening for X-ALD in Italy is feasible and enables early detection and intervention. Biochemical markers and genetic analysis are reliable tools for identifying affected males and female carriers. Multidisciplinary management is essential to address medical and psychosocial challenges during follow-up.

Newborn screening (NBS) for X‐linked adrenoleukodystrophy (ALD) enables early identification of boys at risk for adrenal insufficiency (AI) and cerebral ALD (CALD). However, NBS frequently identifies ABCD1 variants of uncertain significance (VUS), which are associated with only borderline‐elevated C26:0‐lysophosphatidylcholine (LPC(26:0)) levels. Traditional American College of Medical Genetics and Genomics (ACMG) pathogenicity classification does not account for age‐dependent penetrance or the broader phenotypic spectrum, complicating risk assessment and clinical management. Through the Grey Zone Project, we developed a risk‐stratification framework using a receiver operating characteristic (ROC)‐based approach prioritizing 95% sensitivity. This framework incorporates biochemical and longitudinal clinical data from 1627 control subjects and 196 confirmed ALD patients. Three pediatric risk categories were defined: “no ALD” (177 nmol/L). When applied to 108 samples carrying 51 unique ABCD1 VUSs, 26 variants were reclassified as “no ALD,” 15 as “lower‐risk AI/CALD,” and 10 as “at‐risk AI/CALD.” The framework reclassifies ABCD1 variants based on biochemical risk profiles, reducing false‐positive referrals, avoiding unnecessary MRI surveillance, and alleviating parental anxiety by identifying children who are unlikely to develop childhood‐onset disease. Integrating biochemical thresholds with genetic and longitudinal clinical data improves the specificity of NBS without compromising its sensitivity. Providing systematic feedback on false‐positive cases to screening laboratories will further refine cut‐offs. This framework provides a scalable, evidence‐based model for interpreting variants and enabling personalized follow‐up in ALD and other disorders with a variable age of onset.

Background: Allan‐Herndon‐Dudley syndrome (AHDS)/monocarboxylate transporter 8 (MCT8) deficiency is a rare X‐linked encephalopathy caused by SLC16A2 variants, impairing thyroid hormone (TH) transport into the brain. This leads to early central nervous system (CNS) TH deficiency, affecting brain maturation. Dopaminergic circuit involvement is suggested by both pathophysiology and clinical features, reminiscent of infantile parkinsonism. Objective: This study investigates dopamine metabolism and levodopa/carbidopa response in MCT8 patients. Methods: We retrospectively and prospectively collected clinical, genetic, and neuroimaging data, performed cerebrospinal fluid (CSF) biogenic amine analyses, and conducted neurological assessments before and after the levodopa trial (10 mg/kg/day). Results: Ten patients exhibited developmental delay, spasticity, and infantile parkinsonism. CSF analysis showed reduced homovanillic acid in 3/10 patients, with 7/10 in the lowest quartile. Levodopa improved parkinsonism and reactivity in 7/10 patients. Conclusions: Our findings confirm dopaminergic involvement in AHDS and show that levodopa/carbidopa effectively treats extrapyramidal symptoms. Further investigations could differentiate presynaptic and postsynaptic defects to optimize dopaminergic therapy. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.