bims-curels Biomed News
on Leigh syndrome
Issue of 2025–12–14
nine papers selected by
Cure Mito Foundation
  1. Fatal Presentation of Leigh Syndrome in a Neonate: Comprehensive Neuroimaging Findings With MT-ND5 Mutation.
  2. Mitigating Limited Data Challenges to Improve Artificial Intelligence Integration in Rare Disease Drug Development.
  3. Models of Relational Medical Decision-Making: Caregivers and Advanced Life-Sustaining Treatment.
  4. What patients and caregivers want to know when consenting to the use of digital behavioral markers.
  5. Are There Best Ways to Respond to a Patient With an AI-Generated Answer You May Disagree With?
  6. A Taste of Our Own Medicine: Fostering Empathy in Medical Learners Through Patient Simulation.
  7. Letter to the Editor: CRISPR-based gene editing for cardiac protection in Barth syndrome.
  8. Why not knowing can be a virtue.
  9. Challenges associated with disclosing results from whole genome sequencing to diagnose paediatric rare diseases: analysis of parent-clinician interactions.
  1. Cureus. 2025 Nov;17(11): e96098
    Fatal Presentation of Leigh Syndrome in a Neonate: Comprehensive Neuroimaging Findings With MT-ND5 Mutation.
    Shrinivas Radder, Nivedita Radder.
      Leigh syndrome represents a severe mitochondrial disorder characterized by progressive neurodegeneration, typically manifesting in infancy with devastating outcomes. We present a 30-day-old male infant who presented with acute neurological deterioration, including seizures, dystonia, and respiratory failure. Laboratory evaluation revealed elevated levels of lactate and pyruvate. Brain magnetic resonance imaging (MRI) demonstrated characteristic bilateral symmetric T2 hyperintensity with restricted diffusion involving the basal ganglia, thalami, brainstem structures, and multiple other regions. Single-voxel spectroscopy confirmed an elevated lactate peak in the basal ganglia. Genetic testing identified a 95% heteroplasmic pathogenic variant in MT-ND5, confirming mitochondrial DNA-associated Leigh syndrome. Despite intensive supportive care including mechanical ventilation and anticonvulsant therapy, the patient's condition progressively deteriorated, resulting in death 16 days after admission. This case highlights the fulminant presentation of neonatal Leigh syndrome and emphasizes the critical role of neuroimaging in establishing this diagnosis, particularly when combined with biochemical and genetic findings.
    Keywords:  leigh syndrome; mitochondrial disorder; mr spectroscopy; mt-nd5 mutation; neonatal encephalopathy; neuroimaging
    DOI:  https://doi.org/10.7759/cureus.96098
  2. NEJM AI. 2025 Nov 24. pii: AIp2500802. [Epub ahead of print]2(12):
    Mitigating Limited Data Challenges to Improve Artificial Intelligence Integration in Rare Disease Drug Development.
    Atasi Poddar, Gabriel K Innes, Qi Liu, Anindita Saha, Morgan Hanger, Kelly Franzetti, M Khair ElZarrad, Tala H Fakhouri.
      The Orphan Drug Act defines a rare disease as a condition affecting fewer than 200,000 people in the United States. However, most rare diseases are categorized as ultrarare or hyper-rare, impacting fewer than 100 individuals worldwide. Developing drugs for these conditions involves multiple challenges, such as geographically dispersed and small patient populations, limited natural history data, and poor disease characterization. Issues related to small patient numbers, scarce natural history information, and clinical heterogeneity within rare diseases can be addressed by various strategies, including using artificial intelligence and advanced analytical methods, leveraging detailed individual-level data, and exploring synthetic data generation to overcome the limitations of small datasets. Moreover, establishing centralized databases and promoting public-private partnerships can help build a more comprehensive repository of available data.
    DOI:  https://doi.org/10.1056/AIp2500802
  3. Hastings Cent Rep. 2025 Nov-Dec;55(6):55(6): 12-23
    Models of Relational Medical Decision-Making: Caregivers and Advanced Life-Sustaining Treatment.
    Aaron Wightman, Georgina D Campelia.
      Health care faces a rising population of patients with reliance on advanced technologies to sustain life, such as ventricular assist devices. Caregivers are so essential to the success of the technology and patient well-being that the establishment of a reliable caregiver outside of the hospital is standardly required before these technologies are offered. Making the choice to engage in the relationships of care required by the use of advanced life-sustaining technologies (ALSTs) is a significant decision, one that is often taken up out of necessity but also in the context of a loving and caring relationship. However, the value of caregivers, as well as the benefits and burdens of their care labor, can easily be neglected in a decision-making process that focuses on patients alone. Research has repeatedly recommended a more just recognition of the care work in the context of ALST, but few models for involving caregivers alongside patients in shared decision-making exist. We offer a taxonomy of possible models for recognizing the impact and value of care labor in medical decision-making about ALSTs. Ultimately, we recommend a model grounded in care ethics-the care-centered model-because it recognizes and values both the caregiving relationship and the individuals involved.
    Keywords:  ALST; care ethics; caregivers; clinical ethics; medical decision‐making; relational
    DOI:  https://doi.org/10.1002/hast.5004
  4. NPP Digit Psychiatry Neurosci. 2024 Dec 06. 2(1): 19
    What patients and caregivers want to know when consenting to the use of digital behavioral markers.
    Anika Sonig, Christine Deeney, Meghan E Hurley, Eric A Storch, John Herrington, Gabriel Lázaro-Muñoz, Casey J Zampella, Birkan Tunc, Julia Parish-Morris, Jenny Blumenthal-Barby, Kristin Kostick-Quenet.
      Artificial intelligence (AI)-based computational tools for deriving digital behavioral markers are increasingly able to automatically detect clinically relevant patterns in mood and behavior through algorithmic analysis of continuously and passively collected data. The integration of these technologies into clinical care is imminent, most notably in clinical psychology and psychiatry but also other disciplines (e.g., cardiology, neurology, neurosurgery, pain management). Meanwhile, ethical guidelines for implementation are lacking, as are insights into what patients and caregivers want and need to know about these technologies to ensure acceptability and informed consent. In this work, we present qualitative findings from interviews with 40 adolescent patients and their caregivers examining ethical and practical considerations for translating these technologies into clinical care. We observed seven key domains (in order of salience) in stakeholders' informational needs: (1) clinical utility and value; (2) evidence, explainability, evaluation and contestation; (3) accuracy and trustworthiness; (4) data security, privacy, and misuse; (5) patient consent, control, and autonomy; (6) physician-patient relationship; and (7) patient safety, well-being, and dignity. Drawing from these themes, we provide a checklist of questions, as well as suggestions and key challenges, to help researchers and practitioners respond to what stakeholders want to know when integrating these technologies into clinical care and research. Our findings inform participatory approaches to co-designing treatment roadmaps for using these AI-based tools for enhanced patient engagement, acceptability and informed consent.
    DOI:  https://doi.org/10.1038/s44277-024-00022-9
  5. Laryngoscope. 2025 Dec 09.
    Are There Best Ways to Respond to a Patient With an AI-Generated Answer You May Disagree With?
    Priyanka K Bisarya, Katherine A Hom, David B Hom.
      With the increasing use of generative artificial intelligence by patients, discrepancies in discussion can arise during the patient-physician clinic visit. This paper seeks to address practical guidelines for responding during a clinical encounter in which the physician disagrees with an AI-generated medical answer brought forth by a patient.
    Keywords:  artificial intelligence; comprehensive otolaryngology; medical education; patient care; patient education
    DOI:  https://doi.org/10.1002/lary.70307
  6. West J Emerg Med. 2025 Nov 26. 26(6): 1526-1529
    A Taste of Our Own Medicine: Fostering Empathy in Medical Learners Through Patient Simulation.
    Romy Portieles Peña, William Weber.
       INTRODUCTION: Residents and medical students spend thousands of hours of medical education learning the physician's perspective but rarely find themselves on the other side of the stethoscope. In this study we evaluated whether a brief, novel curriculum of simulating the patient experience could improve medical learners' reported empathy for patients and ability to explain medical interventions.
    CURRICULAR DESIGN: Fifty-eight medical learners (medical students and resident physicians) participated in a 50-minute didactic session where learners simulated patient experiences such as wearing a patient gown and cervical collar, walking with crutches, and tasting potassium chloride and thickened water. Learners evaluated their perceptions of the curriculum with a survey.
    IMPACT/EFFECTIVENESS: Participants reported limited experience as patients, with 66.7% never having been hospitalized and 50% not taking any daily medications. Learners rated the curriculum highly on a seven-point Likert scale with 98% expressing it helped them to empathize with patients (90% either agreed or strongly agreed) and 95% expressing that it would help them explain interventions (81% either agreed or strongly agreed). There was no difference between medical students and residents regarding reported effect on empathy (M 6.24 vs 6.44; P = .30) or effect on ability to explain the intervention (M 6.06 vs 6.24; P = .43). This brief curriculum simulating the patient experience was well-received by medical student and resident learners, who overwhelmingly felt it improved their empathy for patients and explanations of common interventions. This approach to fostering empathy could help both medical student and resident learners, many of whom may have limited experience as a patient.
    DOI:  https://doi.org/10.5811/westjem.48535
  7. Ann Med Surg (Lond). 2025 Dec;87(12): 9163-9164
    Letter to the Editor: CRISPR-based gene editing for cardiac protection in Barth syndrome.
    Zain Ul Abedin, Anzah Imtiaz Waggan, Esha Khan, Muhammad Umer Suleman, Syeda Nafisa Tabassum.
      Barth syndrome is a rare X-linked mitochondrial disorder caused by mutations in the Tafazzin (TAZ) gene. These mutations make it hard for cardiolipin to remodel and mitochondria to work properly. This condition is characterized by growth retardation, neutropenia, skeletal myopathy, and dilated cardiomyopathy, frequently leading to significant morbidity and mortality, with numerous patients necessitating heart transplants. There are no treatments available at this time to fix the genetic problem. Recent progress in gene editing, especially CRISPR-based methods, holds great promise for fixing TAZ mutations. Research utilizing patient-derived cardiomyocytes has demonstrated that the rectification of TAZ mutations reinstates mitochondrial efficiency and enhances cellular functionality. Animal models, including TAZ-knockout mice, have exhibited substantial enhancements in cardiac function, survival rates, and diminished fibrosis subsequent to gene replacement therapy.
    Keywords:  adeno-associated virus vectors; barth syndrome; cardiolipins; cardiomyopathy, dilated; crispr-cas systems; gene editing; gene therapy; induced pluripotent stem cells; mitochondrial diseases; myopathy; neutropenia
    DOI:  https://doi.org/10.1097/MS9.0000000000004188
  8. BMJ. 2025 Dec 11. 391 r2592
    Why not knowing can be a virtue.
    Rajeev Dutta.
      
    DOI:  https://doi.org/10.1136/bmj.r2592
  9. J Med Genet. 2025 Dec 11. pii: jmg-2025-111137. [Epub ahead of print]
    Challenges associated with disclosing results from whole genome sequencing to diagnose paediatric rare diseases: analysis of parent-clinician interactions.
    Holly Ellard, Jhumana Ali, Phoebe Buxton, Myra Bluebond-Langner, Celine Lewis.
       BACKGROUND: Whole genome sequencing (WGS) has recently been introduced as a diagnostic test for patients with particular rare diseases in the National Health Service (NHS) in England. Little is known about the process of communicating results from WGS to families in practice.
    METHODS: We audio-recorded clinicians and parents discussing the results of WGS for their child's rare disease diagnosis as part of a larger mixed-methods evaluation of the implementation of the NHS Genomic Medicine Service during its early years.
    RESULTS: 10 consultations were audio-recorded across four NHS Trusts. Clinical indications for WGS were related to neurological and developmental disorders. Seven parents received a genetic diagnosis for their child's condition, two received a variant of uncertain significance, and one received a no primary finding result. One parent also received an incidental finding for their child. Challenges in discussing results included (1) explaining a diagnosis when the genotype was established before detailed phenotyping, (2) navigating follow-up for an adult-onset condition identified in childhood, (3) disclosing an unexpected diagnosis for a parent from trio testing and (4) conveying a diagnosis with an uncertain prognosis.
    CONCLUSION: This study illustrates some of the issues that can arise from unexpected and uncertain information when returning results from broad-scope genomic testing for paediatric neurological and developmental disorders. Further study of actual interactions between clinicians and families discussing results from WGS across different specialities and conditions is needed to inform guidance on communication of results within this rapidly evolving area of medicine.
    Keywords:  Child Health; Genetic Counseling; Genetics, Medical; Genomics; Health Services Research
    DOI:  https://doi.org/10.1136/jmg-2025-111137
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