bims-curels 2026-03-01 papers

bims-curels

Biomed News

on Leigh syndrome

Issue of 2026–03–01
ten papers selected by
Cure Mito Foundation

Nutrient and endocrine factors affecting impaired growth in pediatric mitochondrial diseases.
Generative AI Accelerates Genotype-Phenotype Characterization of a 1600-Case Leigh Syndrome Virtual Cohort from Published Literature.
Empowering patients in family medicine research: a case-study of patient partner involvement in educational and knowledge translation activities.
Profiling mitochondrial DNA indices across whole blood, plasma, and CSF in amyotrophic lateral sclerosis.
Applications of genetic testing in cardiovascular disease.
MITO-VATION: Feasibility of a technology-supported structured home exercise program in Mitochondrial Disease.
Computational Use of Patient-Provider Secure Messaging Data to Achieve Better Clinical Efficiency and Quality of Communication: A Systematic Review.
TikTok as a Platform for Patient Education and Health Information in Rare Genetic Diseases: Cross-Sectional Study.
Next questions of autophagy in neurodegenerative diseases: From mechanisms to therapeutics.
Parental experiences of receiving genomic newborn screening results: findings from the BabyScreen+ study.

Endocrinol Diabetes Metab Case Rep. 2026 Jan 01. pii: EDM250140. [Epub ahead of print]2026(1):

Nutrient and endocrine factors affecting impaired growth in pediatric mitochondrial diseases.

Hideaki Yagasaki, Hiromune Narusawa, Daisuke Watanabe, Fumikazu Sano, Kaoru Fujioka, Sonoko Mizorogi, Yoshimi Kaga, Takeshi Inukai.

   Summary: Mitochondrial diseases cause systemic failure of energy production and can manifest as various disorders of hormone production and secretion from endocrine organs. These effects can prevent normal growth in children, resulting in adults of short stature. We therefore explored the nutritional and endocrinological status of pediatric mitochondrial disease patients with impaired growth. Four Japanese patients with genetically diagnosed mitochondrial disease were studied (one male and three females, aged 4-22 years). The age of onset ranged from 0 months to 7 years, and the causal genes identified were mtDNA, PDHA1, and NARS2 (in two sibling patients). Two patients were diagnosed with small for gestational age at birth, and their current height standard deviation scores ranged from -1.9 SD to -6.4 SD. Mitochondrial diseases can present as impaired growth with dysfunction of various organs, depending on the causal gene and the degree of heteroplasmy. Our patients had demonstrated low T3 syndrome and reduced IGF1 levels, which appeared to be influenced by impaired nutritional status. These findings emphasize the need for careful monitoring of growth trajectories alongside nutritional and endocrine evaluations to improve clinical management.
Learning points: Mitochondrial diseases can disrupt endocrine function involving the GH-IGF1 axis and the thyroid and gonadal systems, leading to impaired growth during childhood. Patients with early-onset mitochondrial disease tend to experience severe symptoms and pronounced growth impairment. Children with mitochondrial diseases often show low IGF1 levels, low T3 syndrome, and delayed bone age, reflecting endocrine dysfunction commonly observed in chronic systemic diseases and the further influence of suboptimal nutritional status.

Keywords:  diabetes; impaired growth; insulin-like growth factor 1; mitochondria

DOI:  https://doi.org/10.1530/EDM-25-0140
Biology (Basel). 2026 Feb 14. pii: 334. [Epub ahead of print]15(4):

Generative AI Accelerates Genotype-Phenotype Characterization of a 1600-Case Leigh Syndrome Virtual Cohort from Published Literature.

Lishuang Shen.

  Leigh Syndrome Spectrum (LSS) is a rare and heterogeneous disease continuum with most published cohorts in small sizes that limit the statistical power. Large-scale meta-analyses with published case-level clinical data extracted from the literature are essential for robust population analysis but are hindered by the burden of manually standardizing the unstructured, heterogeneous, and sparse case-level data from the literature. We developed a novel workflow which is among the first to combine Generative AI (GenAI) with human-in-the-loop curation to overcome this barrier. This pipeline utilized Google's Gemini-2.5-pro and rapidly processed over 2300 cases from published case data tables in two weeks and achieved >90% accuracy in mapping raw clinical data to Human Phenotype Ontology (HPO) terms. This process rapidly yielded a harmonized LSS virtual cohort of 1679 data-rich cases, which is the largest LSS virtual cohort reported so far, and thus enables characterization of LSS phenotypic and genetic architectures, revealing that autosomal recessive (932 cases) and mitochondrial (752 cases) inheritance are the most common. The most frequently mutated genes were SURF1 (240 cases), MT-ATP6 (199), and MT-ND3 (183). HPO term consolidation identified common hallmark phenotypes, including lactic acidosis, hypotonia, bilateral basal ganglia lesions, and mitochondrial respiratory chain deficiency. The cohort's scale enabled large-scale survival analysis, revealing that defects in mitochondrial translation are associated with the poorest prognosis (84% mortality in this group) and early onset (0.23 years). Among the deceased group, patients with Complex V mutations were linked to a significantly shorter mean survival time (1.77 years) than those with Complex I (3.70 years) or IV (3.57 years) mutations. This GenAI-driven methodology establishes a scalable framework for rapidly creating analysis-ready virtual cohorts from heterogeneous literature and accelerating population-level study for rare diseases including Leigh Syndrome and other mitochondrial diseases.

Keywords:  Leigh Syndrome Spectrum (LSS); Leigh disease; generative AI (GenAI); human phenotype ontology (HPO); large language model; rare disease

DOI:  https://doi.org/10.3390/biology15040334
Res Involv Engagem. 2026 Feb 26. pii: 25. [Epub ahead of print]12(1):

Empowering patients in family medicine research: a case-study of patient partner involvement in educational and knowledge translation activities.

Maddie J Venables, Sarah Dickson, Maryame Ichiba, Ali Arrhaoui, Emilie Lamontagne, Kimberly P Grattan, Sharon Johnston, William Hogg, Douglas Archibald.



Keywords:  Medical education; Patient co-design; Patient engagement; Patient-oriented research

DOI:  https://doi.org/10.1186/s40900-026-00841-4
J Neurol Sci. 2026 Feb 06. pii: S0022-510X(26)00079-1. [Epub ahead of print]483 125797

Profiling mitochondrial DNA indices across whole blood, plasma, and CSF in amyotrophic lateral sclerosis.

Jiongming Bai, Xinyuan Pang, Hongfen Wang, Ying Zhang, Yahui Zhu, Jiarui Zhao, Yifan Li, Mao Li, Xusheng Huang.

   BACKGROUND: Recent studies increasingly implicate mitochondrial DNA (mtDNA) alterations in neurodegenerative diseases, but findings across studies remain inconsistent. We aimed to characterize mtDNA indices across whole blood, plasma and CSF compartments and evaluate their clinical relevance.
METHODS: We enrolled two study cohorts: (1) a whole blood cohort of 102 ALS patients; and (2) a plasma and cerebrospinal fluid (CSF) cohort including 132 ALS patients and 62 non-neurodegenerative controls. The D-loop and COX3 regions were selected as representative mtDNA fragments, while B2M was used as a nuclear reference. Quantification was performed using SYBR Green-based quantitative PCR.
RESULTS: In whole blood, higher D-loop/COX3 ratios were associated with better functional status and longer survival. In the cell-free compartments, CSF ccf-mtDNA markers (D-loop and COX3) were significantly higher in ALS than in controls, whereas plasma abundance showed no significant group difference. Within ALS, higher ccf-mtDNA indices tended to correlate with greater disease severity and more rapid functional decline. In addition, higher plasma and CSF D-loop/COX3 ratios showed marginal trends toward association with faster disease progression.
CONCLUSIONS: This study systematically characterizes mtDNA alterations in whole blood, plasma and CSF samples of ALS, offering new insights into mtDNA involvement in neurodegeneration.

Keywords:  Amyotrophic lateral sclerosis (ALS); Circulating cell-free mitochondrial DNA (ccf-mtDNA); Mitochondrial dysfunction; mtDNA copy number

DOI:  https://doi.org/10.1016/j.jns.2026.125797
Curr Opin Cardiol. 2026 Feb 24.

Applications of genetic testing in cardiovascular disease.

Alexandra Smirnova, Mario Urtis, Eloisa Arbustini.

   PURPOSE OF REVIEW: The identification of the genetic basis of an increasing number of cardiovascular diseases (CVDs) has substantially expanded the clinical demand for genetic testing. This review summarizes the major groups of genetic CVDs, the current testing strategies, the limitations of available approaches, and future perspectives for improving diagnostic accuracy.
RECENT FINDINGS: Growing awareness of genetic CVD has stimulated comprehensive clinical phenotyping, family screening, and the integration of advanced imaging, functional studies, and pathological investigations. This has enabled an unprecedented incorporation of genetics into clinical cardiology, representing one of the most transformative developments in the field. This evolution is occurring within multidisciplinary frameworks, generating a high demand for expertise and technological innovation.
SUMMARY: Mendelian CVDs include cardiomyopathies, arrhythmias, arteriopathies, primary calcific CVD, pulmonary hypertension, hereditary hemorrhagic telangiectasia, monogenic vasculitides, autoinflammatory disorders, syndromic cardiovascular tumors, and metabolic diseases (hypercholesterolemia and MODY). Mendelian CVDs are complemented by maternally-inherited mitochondrial diseases, characterized by heterogeneous, often syndromic phenotypes with frequent cardiovascular involvement. The genetic testing landscape is rapidly expanding, aiming to provide comprehensive and simplified "all-in-one" solutions while improving accessibility and sustainability. Key challenges remain related to technological limitations, result interpretation, and test completeness, representing major priorities for future development in cardiovascular genetics.

Keywords:  cardiovascular genetics; genetic cardiovascular diseases; genetic test; precise diagnosis; second- and third-generation sequencing

DOI:  https://doi.org/10.1097/HCO.0000000000001281
PLOS Digit Health. 2026 Feb;5(2): e0001257

MITO-VATION: Feasibility of a technology-supported structured home exercise program in Mitochondrial Disease.

Jeremey Thomas Horne, Natalie E Allen, Serene S Paul, Judith Walker, Carolyn Sue.

Exercise intolerance, combined with low levels of physical activity, are commonly observed in individuals with Primary Mitochondrial Disease (PMD). However, access to health professionals with expertise in prescribing exercise to this population is limited. The use of digital health technology (DHT) may be a feasible and acceptable approach for therapists to support people with PMD to increase levels of physical activity, including exercise. Ten participants with mild to moderate PMD were recruited. All were provided with an eight-week home exercise program via an online exercise prescription app and remotely monitored using a smart watch. Participants received telehealth supporting their home exercise regimen along with reminders to move from the smart watch. The primary outcomes were feasibility and acceptability. Secondary outcomes were physical performance measures and fatigue, measured pre- and post-intervention. Only 26% of eligible participants enrolled. There were no dropouts, and four minor adverse events reported. Most participants (80%) participated in 80% or more of the telehealth sessions and wore the smart watch on 80% or more days during the study. Daily step target achievement was poor and only one participant met their individualised target on ≥80% of days. Half the participants achieved their weekly target of 150 intensity minutes (heart rate >50% of their theoretical maximal heart rate) on 7 or more weeks. Home exercise program adherence was low with only 30% of participants completing 80% or more of the scheduled strength training sessions over 8 weeks. Post-hoc exploration found pre-intervention exercisers achieved 4 out of 5 intervention targets compared to 0 for non-exercisers. Acceptability outcomes extracted from post-program questionnaires were overall positive towards the smart watch and home exercise program. There were no meaningful changes in any physical outcome measures or fatigue post-test. The use of DHT may be feasible and acceptable for prescribing home exercise and monitoring activity levels in individuals with mild to moderate forms of PMD, particularly those with a history of exercise.

DOI: https://doi.org/10.1371/journal.pdig.0001257
AMIA Annu Symp Proc. 2024 ;2024 403-412

Computational Use of Patient-Provider Secure Messaging Data to Achieve Better Clinical Efficiency and Quality of Communication: A Systematic Review.

Yawen Guo, Di Hu, Yiliang Zhou, Tianchu Lyu, Kai Zheng.

Secure messaging (SM) between patients and providers has seen increasing adoption over the past decade, prompting development of computational methods to enable automation and research to enhance clinical efficiency and quality of communication. Through a systematic review, we examined the extant literature to investigate how previous studies had applied computational analyses to SM data. After screening 1,374 papers, we identified 19 relevant studies published between 2017 and 2024, most of which focused on applications for streamlining clinical workflows, facilitating early disease detection, supporting personalized decision making, and enhancing patient health literacy. Among the computational methods used, BERT was consistently shown to deliver best performance. However, all existing studies were constrained by small-size datasets and limited healthcare settings, leading to inadequate validation and poor generalizability. The results of this review highlight key research gaps, particularly the need for more robust computational approaches that ensure scalability, fairness, and clinical applicability.

Keywords: computational methods; patient–provider communication; secure messaging; systematic review
JMIR Form Res. 2026 Feb 24. 10 e79978

TikTok as a Platform for Patient Education and Health Information in Rare Genetic Diseases: Cross-Sectional Study.

Jackson Montgomery Wahman, Rhoda Mariam Hijazi, Hosam Gharib Abdelhady.

   Background: Rare genetic diseases pose significant diagnostic and therapeutic challenges, often leading to delayed diagnoses, misinformation, and patient isolation. Social media platforms have emerged as prominent spaces for health information dissemination and community building among patients with rare diseases.
Objective: This study aimed to evaluate the role of TikTok videos in patient education, community engagement, and information quality related to 5 rare genetic conditions: Ehlers-Danlos syndrome, Marfan syndrome, cystic fibrosis, Wilson disease, and Gaucher disease.
Methods: A cross-sectional analysis was conducted on 184 TikTok videos identified via disease-specific hashtags. Included videos were 15 seconds to 4 minutes long and directly discussed the target diseases. Advertisements, promotional content, and product marketing were excluded. Videos were categorized by creator type: physicians, medical professionals, patients, influencers, nonprofit organizations, and others. Content quality was assessed using the Global Quality Scale (GQS) and a modified DISCERN tool (mDISCERN). Engagement metrics (views, likes, and shares) were recorded. Kruskal-Wallis and chi-square tests evaluated differences across creator categories.
Results: Of the 184 TikTok videos, 88 (47.8%) were created by patients or family members; 31 (16.8%) by influencers, 24 (13.0%) by physicians, 17 (9.2%) by nonprofit organizations, 15 (8.2%) by general users, and 9 (4.9%) by others. Collectively, the videos amassed more than 123 million views. Influencer-generated content accounted for the highest cumulative view count, totaling approximately 60.9 million views. Content produced by medical professionals and physicians demonstrated higher information quality, with mean GQS scores of 3.89 (SD 0.66) and 3.62 (SD 0.71) and mDISCERN scores of 3.11 (SD 0.58) and 3.21 (SD 0.65), respectively. In contrast, videos by influencers and patients exhibited lower quality scores (influencers: GQS mean 1.48, SD 0.60; mDISCERN mean 1.42, SD 0.55; patients: GQS mean 1.57, SD 0.58; mDISCERN mean 1.38, SD 0.52). For Ehlers-Danlos syndrome (n=40 videos, 21.7%), Wilson disease (n=40 videos, 21.7%), and cystic fibrosis (n=34 videos, 18.5%), significant differences in quality scores among creator types were observed (P<.001, P<.001, and P≤.04, respectively). For Marfan syndrome (n=40 videos, 21.7%) and Gaucher disease (n=30 videos, 16.3%), no significant differences were observed (P=.43 and P=.07, respectively). Chi-square analysis indicated no association between creator type and inclusion of peer-reviewed references (χ25=10.6; P=.07). Overall, only 7 (3.8%) videos cited scientific literature.
Conclusions: TikTok serves as a key platform for rare disease awareness and community engagement, although the quality and accuracy of health information vary widely. Although medical professionals produced higher-quality content, it tended to receive less visibility. Increasing the presence of health care professionals and improving visibility of evidence-based content could enhance patient education and safer health information sharing.

Keywords:  Ehlers-Danlos syndrome; Gaucher disease; Marfan syndrome; TikTok; cystic fibrosis; health misinformation; patient education; rare diseases; social media

DOI:  https://doi.org/10.2196/79978
Innovation (Camb). 2026 Jan 05. 7(1): 100989

Next questions of autophagy in neurodegenerative diseases: From mechanisms to therapeutics.

Rongcan Luo.

Autophagy, a key cellular degradation pathway, is central to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Despite progress in understanding its role, critical questions remain. This perspective highlights pressing issues, including cell-type-specific autophagy regulation, interactions with other cellular pathways, and challenges in translating autophagy-modulating therapies to clinical practice. Addressing these questions will advance our understanding of neurodegenerative diseases and pave the way for novel therapeutics.

DOI: https://doi.org/10.1016/j.xinn.2025.100989
Eur J Hum Genet. 2026 Feb 24.

Parental experiences of receiving genomic newborn screening results: findings from the BabyScreen+ study.

Erin Tutty, Anaita Kanga-Parabia, Nathasha Kugenthiran, Jade Caruana, Lilian Downie, Clara Gaff, Nitzan Lang, Sebastian Lunke, Katrina Scarff, Zornitza Stark, Stephanie Best, Alison D Archibald.

Genomic newborn screening (gNBS) provides the potential to offer significant health benefits. However, more evidence, including psychosocial impacts on parents, is needed before gNBS is ready for population-level implementation. The aim of this qualitative study was to explore parental experiences of receiving gNBS results from a prospective study, BabyScreen+. BabyScreen+ screened 1000 newborns for >600 genetic conditions that were early-onset, severe, and had management options available (prevention, surveillance or treatment). We interviewed parents three months after receiving their result. Interviews were analysed using reflexive thematic analysis, guided by Interpretive Description. Twenty-seven parents were interviewed, including nine who received a 'high chance' result for their newborn. Waiting for gNBS results was not unduly anxiety provoking. Low chance results provided psychosocial benefits including peace-of-mind and empowerment. Receiving a high chance result was unexpected and shocking, especially if the result was for a condition with significant treatment recommendations (e.g., transplantation). Psychosocial adaption to the subsequent diagnosis was an evolving process; access to genetic counselling, high-quality information and prompt referrals to specialists increased confidence in managing the condition and facilitated adaptation. All parents valued the high chance gNBS result given its clinical utility. The study provides support for gNBS by highlighting that it can provide valuable health information with minimal harms. Findings can be used to inform the implementation of population-scale gNBS.

DOI: https://doi.org/10.1038/s41431-026-02036-7