bims-curels Biomed News
on Leigh syndrome
Issue of 2026–03–08
eleven papers selected by
Cure Mito Foundation



  1. Genet Med. 2026 Jan;pii: S1098-3600(25)00267-9. [Epub ahead of print]28(1): 101620
       PURPOSE: Primary mitochondrial diseases (PMD) arise from variants in the mitochondrial or nuclear genomes. Phenotype-based recognition of specific PMD genotypes remains difficult, prolonging the diagnostic odyssey. We expanded the MitoPhen database to characterize phenotypic variation across PMD more systematically.
    METHODS: Individual-level data on mitochondrial DNA disorders, nuclear-encoded mitochondrial diseases, and single large-scale mitochondrial DNA deletions were manually curated with Human Phenotype Ontology (HPO) terms to produce MitoPhen v2. Principal-component analysis summarized system-level abnormalities; HPO-level enrichment and mean phenotype-similarity scores were then used to distinguish common PMD genotypes.
    RESULTS: MitoPhen v2 adds 3940 individuals to the original release, now encompassing 1597 publications, 10,626 individuals, and 117 genotypes. Among 7586 affected cases, 72,861 HPO terms were recorded. Principal-component analysis revealed 6 phenotype dimensions capturing most system-level variance. At the HPO level, we observed genotype-specific enrichments and identified 111 gene-phenotype links absent from the current HPO database. Using MT-TL1, single large-scale mitochondrial DNA deletions, and POLG as exemplars, phenotype-similarity scores reliably separated individuals with these genotypes from those without.
    CONCLUSION: MitoPhen v2 enabled systematic, genotype-aware analysis of heterogeneous PMD phenotypes and highlighted the diagnostic value of structured, individual-level data. Phenotype-similarity metrics from such data sets can refine variant interpretation in large rare-disease cohorts and provide a transferable framework for other phenotypically complex genetic disorders.
    Keywords:  HPO; Mitochondrial disease; Phenotype similarity; Rare disease; UMAP
    DOI:  https://doi.org/10.1016/j.gim.2025.101620
  2. Zhongguo Dang Dai Er Ke Za Zhi. 2026 Feb 15. pii: 1008-8830(2026)02-0250-07. [Epub ahead of print]28(2): 250-256
      This report describes the potential diagnostic value of decreased plasma citrulline (pCit) levels for the early recognition of MT-ATP6-related mitochondrial disease. Two cases were reported, and relevant literature was reviewed. Case 1: Onset occurred at 3 months of age with an acute presentation that rapidly progressed to metabolic crisis, multiorgan failure, and central respiratory failure, resulting in death in early infancy. Case 2: Onset occurred at 6 months of age with progressive developmental delay. Brain magnetic resonance imaging revealed bilateral symmetric basal ganglia lesions, and Leigh syndrome was diagnosed. Following citrulline supplementation and comprehensive intervention, improvements were observed in intellectual development and metabolic indices. Both patients carried the MT-ATP6 variant m.8993T>G (p.L156R), confirming MT-ATP6-associated mitochondrial disease. This case series indicates that decreased pCit on newborn screening is an early biochemical marker of MT-ATP6-associated mitochondrial disease. Early diagnosis and metabolic intervention are beneficial for prognosis.
    Keywords:  Hypocitrullinemia; MT- ATP6; Mitochondrial disease; Newborn screening; m.8993T>G
    DOI:  https://doi.org/10.7499/j.issn.1008-8830.2505143
  3. Seizure. 2026 Feb 18. pii: S1059-1311(26)00050-6. [Epub ahead of print]
      Primary mitochondrial diseases are caused by mutations in genes required for expression, function or assembly of the mitochondrial oxidative phosphorylation system. The pathology of primary mitochondrial diseases is varied and a subset of these are associated with epilepsy and seizures. Mutations are found in each of the 5 complexes of the oxidative phosphorylation system in both structural subunits and assembly factors along with mitochondrially encoded components of the protein synthesis machinery. This review will highlight the mutations identified in clinical case studies that are associated with epilepsy and seizures and include the studies using cell systems and other model organisms where molecular characterisation of oxidative phosphorylation is more extensive. The molecular causes of epilepsy have not been well characterised in the relevant cells. This review identifies gaps in knowledge and suggestions for future studies to advance the understanding of the molecular pathogenesis of epilepsy that is associated with primary mitochondrial disease.
    Keywords:  Biogenesis; Electron transport chain; Epilepsy; Mitochondria; Oxidative phosphorylation; Seizures
    DOI:  https://doi.org/10.1016/j.seizure.2026.02.016
  4. Autoimmun Rev. 2026 Feb 28. pii: S1568-9972(26)00025-X. [Epub ahead of print]25(3): 104011
      Mitochondria exhibit tissue-specific physiological functions and are central to the maintenance of cellular homeostasis. Emerging evidence indicates that intercellular mitochondrial transfer is regulated by multiple determinants and exerts a profound influence on the function of both innate and adaptive immune cells. The underlying mechanisms are highly heterogeneous, involving distinct cellular contexts, microenvironmental cues, and modes of intercellular communication. This review summarizes the major triggers and mechanistic pathways governing mitochondrial transfer in immune cells and immune-related diseases, and discusses the therapeutic potential of this process while highlighting key challenges that currently limit its clinical translation. By integrating recent mechanistic insights and translational perspectives, this review aims to provide a conceptual framework for the development of mitochondrial transfer-based strategies in the treatment of immune-mediated disorders.
    Keywords:  Immune cells; Mitochondrial transfer; Neutrophils; T cells
    DOI:  https://doi.org/10.1016/j.autrev.2026.104011
  5. Clin Teach. 2026 Apr;23(2): e70382
      Researchers are increasingly expected to demonstrate that their work leads to impact beyond academia, particularly when seeking research funding. Yet practical guidance on how to plan for, achieve and evidence impact in Clinical Education Research (ClinEdR) remains limited. This guide offers pragmatic advice to support postdoctoral researchers in designing fundable projects and producing work that leads to meaningful change. We argue that impact should be considered from the start of a research project, not added at the end. Early and ongoing engagement with potential research beneficiaries, including educators, learners, institutions, professional bodies, policymakers and patients, helps ensure that research addresses real-world priorities. Such engagement can shape research questions, study design and outputs, strengthening both grant applications and the likelihood of downstream uptake. This how to guide outlines the value of articulating a clear impact goal and mapping a credible pathway to impact that distinguishes between outputs, outcomes and longer term benefits. We discuss how methodological choices can enable impact, with attention to participatory, design-based and implementation-focused approaches that have change embedded within them. We also highlight the importance of embedding impact checkpoints throughout a project, recognising that impact is often non-linear, delayed and context dependent. Finally, we describe deliberate, audience-specific dissemination strategies and practical ways to evidence impact beyond traditional academic metrics. Embedding impact thinking across the research lifecycle can enhance the relevance, reach and value of ClinEdR, while supporting postdoctoral researchers to meet funder, institutional and societal expectations.
    DOI:  https://doi.org/10.1111/tct.70382
  6. Perspect Med Educ. 2026 ;15(1): 188-199
       Introduction: Shared decision-making, in which a patient's values and preferences facilitate the co-construction of a clinical decision, is a key component of patient-centered care and is of pedagogical interest in medical training. Yet, barriers exist to implementation, with limited information about how patients understand and exert agency. To help educators and health professionals facilitate shared decision-making, we examined how patients narrate their agentic experiences and the roles of their physician and a decision aid mobile application (app) in contributing to agency when engaged in contraceptive clinical encounters.
    Methods: We conducted a qualitative study of 21 female patients, aged 17-45, who utilized a decision aid app before an encounter for contraceptive services. We conducted linguistic analysis of semi-structured interviews where patients narrated their decision-making experiences, by coding for linguistic markers of agency.
    Results: Patients narrated individual agency, identifying agentive tasks required for decision-making, including gaining knowledge, asking questions, voicing needs, and making choices. Patients narrated the app as a source of information, identifying questions, validating previous knowledge/opinions, and as surrogate provider. Patients narrated physicians as supportive agents, cueing patient agency and actions during the visit. Joint agency of patient and physician and agency distributed across the patient, physician, app, and other resources were contributory.
    Discussion: Linguistic analysis can offer important perspectives on patient experiences. The patient, physician, and decision aid app each played roles as agents during shared decision-making. Attending to various roles of agency in clinical encounters and in educational interventions may help health professionals more effectively conduct shared decision-making.
    DOI:  https://doi.org/10.5334/pme.2372
  7. Front Neurosci. 2026 ;20 1764964
      Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) have become major global causes of disability and mortality. Their complex pathogenic mechanisms remain incompletely understood, and effective disease-modifying therapies are still lacking. Traditional animal models and two-dimensional (2D) cell culture systems exhibit notable limitations in structural complexity, human relevance, and translational validity, making it difficult to faithfully recapitulate human-specific neuropathology. In recent years, brain organoid technology derived from induced pluripotent stem cells (iPSCs) has advanced rapidly, enabling the self-organization of diverse neuronal and glial cell types within a three-dimensional (3D) architecture that partially mimics human brain development and disease-related pathological events. When integrated with CRISPR-Cas9-based genome editing and multi-omics profiling, organoids support causal mechanism studies, target validation, and individualized drug-response prediction, highlighting their growing value in early-stage drug discovery. Despite current challenges-including insufficient maturation, lack of vascularization and immune components, and batch variability-the continuous progress in bioengineering, microfluidic systems, and artificial intelligence (AI)-driven multimodal data analysis is steadily expanding the translational potential of organoids as human-relevant preclinical models. Overall, brain organoids provide an essential foundation for constructing physiologically relevant and predictive research platforms for neurodegenerative diseases, offering new opportunities for therapeutic development and precision medicine.
    Keywords:  CRISPR-Cas9 genome editing; brain organoids; drug discovery; induced pluripotent stem cells (iPSCs); neurodegenerative diseases
    DOI:  https://doi.org/10.3389/fnins.2026.1764964
  8. Cureus. 2026 Jan;18(1): e102392
      Enoyl-CoA hydratase short-chain 1 (ECHS1) variants are among the most common causes of Leigh syndrome. A five-year-old boy with ECHS1 deficiency initially presented with acute encephalopathy during the neonatal period. The patient had a high serum lactate level and a normal lactate/pyruvate ratio. Diffusion-weighted imaging showed reduced diffusion in the peri-rolandic subcortical white matter on day 3 and in the entire cortex and subcortical white matter on day 7. The patient subsequently presented with poor feeding, hypotonia, nystagmus, cerebellar ataxia, hearing loss, and strabismus. At one year of age, neuroimaging revealed reduced diffusion, hyperperfusion on arterial spin labeling, and increased lactate on magnetic resonance (MR) spectroscopy in the cerebellum. Cerebellar lesions have not previously been reported as imaging findings of ECHS1 deficiency except in one previous report of a patient with the same ECHS1 variant. Therefore, the ECHS1variant may specifically involve the cerebellum.
    Keywords:  arterial spin labeling; cerebellum; echs1; leigh syndrome; magnetic resonance spectroscopy; valine
    DOI:  https://doi.org/10.7759/cureus.102392
  9. Qual Life Res. 2026 Mar 04. pii: 90. [Epub ahead of print]35(4):
      
    Keywords:  PPI; Patient advocacy; Patient engagement; Research ethics; Shared decision making
    DOI:  https://doi.org/10.1007/s11136-026-04187-y
  10. BMC Med Inform Decis Mak. 2026 Mar 02. pii: 60. [Epub ahead of print]26(1):
      
    Keywords:  Data quality; EHR data; ETL; FAIR guiding principles; HL7 FHIR; Healthcare standards; Hospital information system; Interoperability; Medical data integration; Rare Diseases; Semantic annotation
    DOI:  https://doi.org/10.1186/s12911-025-03153-x