Rare diseases, also known as orphan diseases, are a group of disorders that affect a small percentage of the population. Despite individually affecting a small number of people, collectively, they impact millions worldwide. This is particularly significant in paediatric patients, highlighting the global scale of the issue. This review delves into the exact prevalence of rare diseases among children and adolescents and their diverse impact on the quality of life of patients and their families. The review sheds light on the complex interplay of genetic and environmental factors contributing to these conditions and the diagnostic challenges and delays often encountered in identifying and categorising these diseases. It is noted that although there have been significant strides in the field of genomic medicine and the development of orphan drugs, effective treatments remain limited. This necessitates a comprehensive, multidisciplinary approach to management involving various specialities working closely together to provide holistic care. Furthermore, the review addresses the psychosocial and economic burdens faced by families with paediatric patients suffering from rare diseases, highlighting the urgent need for enhanced support mechanisms. Recent technological and therapeutic advancements, including genomic sequencing and personalized medicine, offer promising avenues for improving patient outcomes. Additionally, the review underscores the role of policy and advocacy in advancing research, ensuring healthcare access, and supporting affected families. It emphasises the importance of increased awareness, education, and collaboration among healthcare providers, researchers, policymakers, and patient advocacy groups. It stresses the pivotal role each group plays in improving the diagnosis, treatment, and overall quality of life for paediatric patients with rare diseases.

GFM1 is a nuclear gene that plays a role in mitochondrial function. In recent decades, various homozygous and compound heterozygous mutations have been identified, leading to significant health issues in patients and often resulting in early death. There is a few experimental research on this gene, particularly regarding its pathogenicity through in silico methods and RNA sequencing and experimental validation in GFM1 knockout cells. This study aims to explore how high-risk pathogenic variants affect protein stability and function using a comprehensive bioinformatics approach. Analyses with Align-GVGD, PolyPhen-2, MupRo, and SIFT indicated that most variants are likely to be highly pathogenic and destabilize the protein structure. The variants were consistently classified as high-risk by Align-GVGD and were deemed "probably damaging" or "possibly damaging" by PolyPhen-2. MupRo analysis suggested a reduction in protein stability, while SIFT indicated functional impacts for all variants. Further analysis with MetaRNN and structural assessments showed that these variants affect protein size, charge, and hydrophobicity, which may disrupt inter-domain interactions and hinder protein function. Differential gene expression analysis in GFM1 knockout HK2 and 293 T cells revealed significant changes in gene expression, particularly in areas related to translation, mitochondrial function, and cellular responses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that the affected genes are linked to neurodegenerative diseases, cancer, and various signaling pathways. GFM1 knockout cells displayed notable pathway changes, including those related to oxidative phosphorylation and neurodegenerative diseases (e.g., Parkinson's, Alzheimer's, Huntington's). Upregulation of mitochondrial electron transport chain components (COX17, NDUFB1, ATP5MC1) suggests a compensatory mechanism in response to impaired mitochondrial function. Disruptions in proteostasis and protein synthesis were highlighted by dysregulated proteasome and ribosomal pathways. Markers of mitophagy, such as increased HSP90 and decreased TOMM20 levels, along with changes in PINK1 protein, emphasize GFM1's involvement in mitophagy. Protein-protein interaction analysis connected GFM1 to key mitophagy proteins (e.g., OPTN, Park2/Parkin). Functional experiments confirmed increased mitophagy, indicating a protective response. These results highlight the negative impact of high-risk pathogenic variants on protein stability and cellular function, shedding light on their potential roles in disease progression. This study offers valuable insights into the pathogenic mechanisms linked to GFM1 mutations, underscoring its critical role in mitochondrial function and cellular balance. The findings highlight the gene's involvement in mitophagy, oxidative phosphorylation, and neurodegenerative pathways, laying the groundwork for future research into therapeutic approaches targeting GFM1-related dysfunctions.

Rare diseases present a significant economic burden on patients, families, and healthcare systems worldwide. As the prevalence of these diseases rises in China, data regarding their impact, specifically in Hainan Province, is scarce. Thus, this study aims to evaluate insurance coverage, economic costs, and the factors contributing to the burden of rare diseases in Hainan. We employed a bottom-up approach to analyse the prevalence and economic burden from 2019 to 2023, utilising data from the Hainan Provincial Health Commission Databases. We assessed insurance coverage as well as expenditures related to hospitalisation, diagnostics, medications, surgery, and out-of-pocket costs. Of 4,975 patients diagnosed with 99 distinct rare diseases, 83.01% were insured. From 2019 to 2023, the number of patients increased from 760 to 1,328, while economic costs surged from 34.26 million CNY (US$ 4.89 million) to 64.74 million CNY (US$ 8.86 million). Thalassemia major, one of the most prevalent conditions, generated the highest costs. Hospitalisation expenses accounted for 49.16% of the total costs, with out-of-pocket expenses averaging 17.52%. The findings reveal a significant economic burden associated with rare diseases in Hainan, highlighting the necessity for targeted policy interventions. Furthermore, additional research is needed to refine estimates of this economic burden.

Background: Mitochondrial encephalomyopathy (ME) is a rare genetic disorder that significantly impacts participants’ quality of life and places emotional and financial burdens on caregivers. However, the dynamics between perceived financial burden, disability, and caregiver strain are not fully understood. This study aimed to explore the differences in perceived financial burden, QoL, disability levels, and caregiver burden among participants with ME.Methods: Between January and December 2023, we conducted a cross-sectional analysis of ME participants and their caregivers at Haikou Affiliated Hospital of Xiangya Medical College, Central South University. Multiple assessment scales, including CHU-9D, PedsQL, PHQ-9, and CBI, were used to evaluate disease burden, QoL, disability, and caregiver burden. Descriptive statistics and correlation coefficients were employed to assess the relationships between these factors.Results: A total of 27 participants with ME were identified, with a mean age of 10.14 years, 88.9% of whom were children. The cohort comprised 18 (66.7%) males and 9 (33.3%) females; MELAS and Leigh syndrome were the most common subtypes. Significant correlations were found between QoL scores and caregiver burden, with CHU-9D showing negative correlations with PHQ-9 and CBI and positive correlations with PedsQL and health utility scores. Additionally, 44.4% of participants reported severe financial burdens, and 57.7% of caregivers experienced moderate to severe levels of burden.Conclusion: Our findings highlight the complex relationships between financial strain, QoL, and caregiver burden in ME. This underscores the need for comprehensive, patient-centered care and targeted policy interventions to alleviate patient and caregiver burdens. Further research is essential to develop effective support systems and improve overall outcomes.

Inherited metabolic disorders (IMDs) comprise more than 1,400 rare genetic conditions affecting paediatric patients worldwide. Despite advances in newborn screening and dietary management, many children experience chronic complications, gastrointestinal symptoms, and reduced health-related quality of life (HRQoL). Emerging evidence—predominantly from phenylketonuria (PKU)—suggests that gut microbiota may influence metabolic homeostasis and patient-centred outcomes in affected children. Because of substantial methodological heterogeneity and the rarity of individual disorders, we elected a narrative review format to synthesise current evidence rather than a formal quantitative synthesis. Electronic searches were performed in PubMed, Embase, and Web of Science from inception to February 2026. We synthesise current evidence regarding gut microbiota composition in major paediatric IMDs, including PKU, organic acidemias, glycogen storage diseases, lysosomal storage disorders, and mitochondrial diseases. For PKU, controlled studies report reduced microbial diversity and depletion of butyrate-producing taxa associated with long-term dietary treatment. For the remaining disorders, direct paediatric microbiome data are sparse or absent, and proposed links rely on mechanistic extrapolation from non-IMD populations. We present the gut microbiota–metabolism–quality of life axis as a conceptual framework that integrates microbial metabolites, intestinal barrier function, immune signalling, and patient-reported outcomes, while emphasising that direct causal evidence linking microbiota alterations to HRQoL in paediatric IMDs is currently lacking. Microbiota-directed interventions remain preliminary. Future multicentre longitudinal studies integrating microbiome profiling, multi-omics technologies, and validated patient-reported outcomes are needed to clarify causal mechanisms and therapeutic potential. Importantly, the available evidence is heterogeneous: direct paediatric microbiome evidence is strongest for PKU, whereas evidence for other IMDs is sparse and often observational, preclinical, or extrapolated from non-IMD populations. The proposed microbiota–metabolism–HRQoL axis is therefore presented as a hypothesis-generating framework rather than an established causal pathway.