bims-curels Biomed News
on Leigh syndrome
Issue of 2024–09–22
six papers selected by
Cure Mito Foundation
  1. Social provisions in patients with mitochondrial diseases.
  2. [Leigh syndrome caused by the mitochondrial m.8993T>G mutation with hypocitrullinemia: a report of four cases and literature review].
  3. Quantitative proteomics of patient fibroblasts reveal biomarkers and diagnostic signatures of mitochondrial disease.
  4. Exploring What Motivates Parents of Children Living With Medical Complexity to Participate in Research.
  5. Using a Previsit Questionnaire for Initial Visits in a Pediatric Mitochondrial Clinic: Perspectives of Parents, a Specialty Physician, and a Clinical Coordinator.
  6. Mitochondrial Health Markers and Obesity-Related Health in Human Population Studies: A Narrative Review of Recent Literature.
  1. BMJ Neurol Open. 2024 ;6(2): e000770
    Social provisions in patients with mitochondrial diseases.
    Sameen Haque, Karen Crawley, Deborah Schofield, Rupendra Shrestha, Ryan Davis, Carolyn M Sue.
       ABSTRACT:
    Background: Mitochondrial diseases often follow a chronic, multimorbid disease course in adults. Like other chronic conditions, mitochondrial diseases present a challenge to public and community health models and patients are potentially at higher risk of social isolation and loneliness. However, there is lack of data on social provisions in mitochondrial diseases.
    Methods: We performed a cross-sectional observational study on patients with a confirmed genetic or clinical diagnosis of mitochondrial disease, recruited between September 2018 and December 2021. Participants completed the Social Provisions Scale (SPS) as a measure of social support. Designated carers similarly completed the SPS in carer-specific questionnaires.
    Results: 95 mitochondrial disease patients and 24 designated carers completed the SPS. Social provisions were met for all six subscales of SPS in the mitochondrial disease cohort: (1) guidance 90.5% (n=86), (2) reassurance of self-worth 82.8% (n=77), (3) social integration 88.4% (n=84), (4) attachment 83.2% (n=79), (5) opportunity of nurturance, 61.1% (n=58) and (6) reliable alliance 95.8% (n=91). All social provisions were also met in the carer cohort.
    Conclusion: Patients with mitochondrial diseases and their carers demonstrate a high perceived level of social support in the setting of a tertiary referral centre specialised in mitochondrial disease despite the burden of chronic disease.
    Keywords:  MITOCHONDRIAL DISORDERS; NEUROEPIDEMIOLOGY; NEUROGENETICS; NEUROMUSCULAR; QUALITY OF LIFE
    DOI:  https://doi.org/10.1136/bmjno-2024-000770
  2. Zhongguo Dang Dai Er Ke Za Zhi. 2024 Sept 15;26(9):pii: 1008-8830(2024)09-0940-06. [Epub ahead of print]26(9): 940-945
    [Leigh syndrome caused by the mitochondrial m.8993T>G mutation with hypocitrullinemia: a report of four cases and literature review].
    Ying-Xue Li, Dong-Juan Wang, Mao-Bin Zhou, Hao-Xuan Sun, Si-Qi Hong, Li Jiang, Yi Guo.
       OBJECTIVES: To explore early diagnostic biological markers for Leigh syndrome caused by the m.8993T>G mutation.
    METHODS: A retrospective analysis was performed on the clinical data of four children diagnosed with m.8993T>G mutation-related mitochondrial disease at the Children's Hospital of Chongqing Medical University from January 2014 to January 2024. Additionally, a literature review was conducted.
    RESULTS: All four children had plasma amino acid and acylcarnitine analyses that revealed decreased citrulline levels, and one child was initially identified through neonatal genetic metabolic disease screening. According to the literature review, there were 26 children with mitochondrial disease and hypocitrullinemia caused by the m.8993T>G mutation (including the four children in this study). Among these, 12 children exhibited clinical phenotypes of Leigh syndrome or Leigh-like syndrome, while 18 children were identified with hypocitrullinemia and/or elevated levels of 3-hydroxyisovalerylcarnitine (C5-OH) during neonatal genetic metabolic disease screening.
    CONCLUSIONS: Hypocitrullinemia may serve as a potential biomarker for the early diagnosis of m.8993T>G mutation-associated Leigh syndrome, detectable as early as during neonatal genetic metabolic disease screening.
    Keywords:  Child; Hypocitrullinemia; Leigh syndrome; MT-ATP6 gene; m.8993T>G
    DOI:  https://doi.org/10.7499/j.issn.1008-8830.2404036
  3. JCI Insight. 2024 Sep 17. pii: e178645. [Epub ahead of print]
    Quantitative proteomics of patient fibroblasts reveal biomarkers and diagnostic signatures of mitochondrial disease.
    Sandrina P Correia, Marco F Moedas, Lucie S Taylor, Karin Naess, Albert Z Lim, Robert McFarland, Zuzanna Kazior, Anastasia Rumyantseva, Rolf Wibom, Martin Engvall, Helene Bruhn, Nicole Lesko, Ákos Végvári, Lukas Käll, Matthias Trost, Charlotte L Alston, Christoph Freyer, Robert W Taylor, Anna Wedell, Anna Wredenberg.
       BACKGROUND: Mitochondrial diseases belong to the group of inborn errors of metabolism (IEM), with a prevalence of 1:2,000-1:5,000. They are the most common form of IEM, but despite advances in next-generation sequencing technologies, almost half of the patients are left genetically undiagnosed.
    METHODS: We investigated a cohort of 61 patients with defined mitochondrial disease to improve diagnostics, identify biomarkers, and correlate metabolic pathways to specific disease groups. Clinical presentations were structured using human phenotype ontology terms, and mass spectrometry-based proteomics was performed on primary fibroblasts. Additionally, we integrated six patients carrying variants of uncertain significance (VUS) to test proteomics as a diagnostic expansion.
    RESULTS: Proteomic profiles from patient samples could be classified according to their biochemical and genetic characteristics, with the expression of five proteins (GPX4, MORF4L1, MOXD1, MSRA and TMED9) correlating with the disease cohort, and thus, acting as putative biomarkers. Pathway analysis showed a deregulation of inflammatory and mitochondrial stress responses. This included the upregulation of glycosphingolipid metabolism and mitochondrial protein import, as well as the downregulation of arachidonic acid metabolism. Furthermore, we could assign pathogenicity to a VUS in MRPS23 by demonstrating the loss of associated mitochondrial ribosome subunits.
    CONCLUSION: We established mass spectrometry-based proteomics on patient fibroblasts as a viable and versatile tool for diagnosing patients with mitochondrial disease.
    FUNDING: The NovoNordisk Foundation, Knut and Alice Wallenberg Foundation, Wellcome Centre for Mitochondrial Research, UK Medical Research Council, and the UK NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children.
    Keywords:  Metabolism; Mitochondria; Molecular diagnosis; Proteomics
    DOI:  https://doi.org/10.1172/jci.insight.178645
  4. Child Care Health Dev. 2024 Sep;50(5): e13331
    Exploring What Motivates Parents of Children Living With Medical Complexity to Participate in Research.
    Laesa Kim, Anne-Mette Hermansen, Karen Cook, Harold Siden.
       BACKGROUND: The study aimed to understand the experience of and identify the motivations for parents participating in health research for their children with medical complexity (CMC). Patient-oriented research strategies are increasingly important in health research to ensure that the voices of patients and parents help shape and direct research programmes. To bring a family-centred and patient-oriented focus to our research and objectives, we asked parents about their experiences when they participated in healthcare research related to their child with CMC.
    METHODS: A parent partner, who also has a CMC, interviewed 12 parents (11 mothers and 1 father) of children living with medical complexity to understand their motivations to participate in healthcare research for their child. The parent partner conducted and transcribed the interviews and led our data analysis. Interpretive phenomenological analysis (IPA) was used to inform our data coding and analytic process.
    RESULTS: Parents described numerous reasons for their participation in research about their children. These motivations landed within four main themes: feeling helpless and hopeful, child-centred motivation, being part of something good and forming a relationship with the research team. In addition to these themes, parents highlighted factors that influenced their ability or desire to participate, such as time, capacity and the level of invasiveness for their child. Ultimately, the reflections by parents emphasized their unique lives in caring for their CMC and the need to integrate their lived experiences with the research they engage in.
    CONCLUSION: This study offers important insights for healthcare teams who want to engage parents of CMC to participate in research. Understanding parents' motivation to participate in research can help researchers create richer engagement and more meaningful experiences for themselves and their participants, thereby bolstering research programmes.
    Keywords:  children with medical complexity; experts with lived experience; non‐verbal children; parents; patient‐oriented research strategies; rare diseases; research participation
    DOI:  https://doi.org/10.1111/cch.13331
  5. J Child Neurol. 2024 Sep 13. 8830738241278388
    Using a Previsit Questionnaire for Initial Visits in a Pediatric Mitochondrial Clinic: Perspectives of Parents, a Specialty Physician, and a Clinical Coordinator.
    Coral J Sepulveda, Elaine Walsh, Kristen Carlin, Russell P Saneto.
      Objective: In this study, we assessed the usefulness of a previsit questionnaire for children who were referred for an initial evaluation in a mitochondrial subspecialty clinic. We explored the themes regarding parent's questions, concerns, and goals. We aimed to add to existing knowledge about the usefulness of previsit questionnaires in a pediatric specialty setting from the perspective of parents, the specialist, and the clinical coordinator. Method: We enrolled 25 patients and their parent(s) over 25 months. Questionnaires were completed by the parent(s), the clinical coordinator, and the mitochondrial specialist. Descriptive statistics and thematic analysis were used to summarize results. Results: Parental responses suggested that they are most concerned about their child's clinical problems, communication, language and developmental delays, disease progression and prognosis, understanding mitochondrial disease, quality of life, and physical challenges including muscle and energy problems. Parents felt the previsit questionnaire was very helpful for both the doctor and for themselves to be prepared for their visit. The specialist and the clinical coordinator also found it to be helpful. Parental comments suggested that they felt that writing down the story of their child's life was helpful for the provider, allowed time for reflection, and improved the appointment experience. Some felt it was a difficult or redundant activity. Conclusion: Parents were often pleased to complete the previsit questionnaire. This allowed them to highlight concerns and share information that they wanted the care team to know about their child. We revised the tool based on feedback from parents and the specialist and will continue to use it in our clinic.
    Keywords:  ambulatory care; mitochondrial disease; parent perspective; pediatric subspecialty clinic; previsit questionnaire
    DOI:  https://doi.org/10.1177/08830738241278388
  6. Curr Obes Rep. 2024 Sep 17.
    Mitochondrial Health Markers and Obesity-Related Health in Human Population Studies: A Narrative Review of Recent Literature.
    Pei Wen Tung, Vidhu V Thaker, Dympna Gallagher, Allison Kupsco.
       PURPOSE OF REVIEW: This narrative review summarizes current literature on the relationship of mitochondrial biomarkers with obesity-related characteristics, including body mass index and body composition.
    RECENT FINDINGS: Mitochondria, as cellular powerhouses, play a pivotal role in energy production and the regulation of metabolic process. Altered mitochondrial functions contribute to obesity, yet evidence of the intricate relationship between mitochondrial dynamics and obesity-related outcomes in human population studies is scarce and warrants further attention. We discuss emerging evidence linking obesity and related health outcomes to impaired oxidative phosphorylation pathways, oxidative stress and mtDNA variants, copy number and methylation, all hallmark of suboptimal mitochondrial function. We also explore the influence of dietary interventions and metabolic and bariatric surgery procedures on restoring mitochondrial attributes of individuals with obesity. Finally, we report on the potential knowledge gaps in the mitochondrial dynamics for human health for future study.
    Keywords:  Adiposity; Bariatric Surgery; Epidemiology; Mitochondrial Biomarkers; Mitochondrial DNA; Obesity
    DOI:  https://doi.org/10.1007/s13679-024-00588-7
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