bims-curels Biomed News
on Leigh syndrome
Issue of 2024–10–06
six papers selected by
Cure Mito Foundation
  1. Mitochondrial Dysfunctions: Genetic and Cellular Implications Revealed by Various Model Organisms.
  2. Stroke-like episodes in patients with adult-onset neuronal intranuclear inclusion disease and patients with late-onset MELAS: A comparative study.
  3. 'The phenotypic conundrum of Trp748Ser variant in POLG gene: a report of two patients'.
  4. Recognizing Leber's Hereditary Optic Neuropathy to avoid delayed diagnosis and misdiagnosis.
  5. What do family caregivers of patients with life-threatening diseases need from healthcare professionals? A qualitative study.
  6. New Insights into Mitochondria in Health and Diseases.
  1. Genes (Basel). 2024 Sep 01. pii: 1153. [Epub ahead of print]15(9):
    Mitochondrial Dysfunctions: Genetic and Cellular Implications Revealed by Various Model Organisms.
    Monika Stańczyk, Natalia Szubart, Roman Maslanka, Renata Zadrag-Tecza.
      Mitochondria play a crucial role in maintaining the energy status and redox homeostasis of eukaryotic cells. They are responsible for the metabolic efficiency of cells, providing both ATP and intermediate metabolic products. They also regulate cell survival and death under stress conditions by controlling the cell response or activating the apoptosis process. This functional diversity of mitochondria indicates their great importance for cellular metabolism. Hence, dysfunctions of these structures are increasingly recognized as an element of the etiology of many human diseases and, therefore, an extremely promising therapeutic target. Mitochondrial dysfunctions can be caused by mutations in both nuclear and mitochondrial DNA, as well as by stress factors or replication errors. Progress in knowledge about the biology of mitochondria, as well as the consequences for the efficiency of the entire organism resulting from the dysfunction of these structures, is achieved through the use of model organisms. They are an invaluable tool for analyzing complex cellular processes, leading to a better understanding of diseases caused by mitochondrial dysfunction. In this work, we review the most commonly used model organisms, discussing both their advantages and limitations in modeling fundamental mitochondrial processes or mitochondrial diseases.
    Keywords:  mitochondria; mitochondrial dysfunction; model organisms
    DOI:  https://doi.org/10.3390/genes15091153
  2. Ann Clin Transl Neurol. 2024 Oct 04.
    Stroke-like episodes in patients with adult-onset neuronal intranuclear inclusion disease and patients with late-onset MELAS: A comparative study.
    Yuzhi Shi, Gehong Dong, Hua Pan, Hongfei Tai, Yi Zhou, An Wang, Songtao Niu, Bin Chen, Xingao Wang, Zaiqiang Zhang.
       OBJECTIVE: To delineate the characteristics of stroke-like episodes (SLEs) in patients with adult-onset neuronal intranuclear inclusion disease (NIID) and to compare these characteristics with those of patients with MELAS.
    METHODS: Twenty-three adult-onset NIID patients who presented with acute or subacute brain disorders and 13 late-onset MELAS patients were enrolled in the study. Patients with NIID were categorized into the SLEs group and the encephalopathy-like episodes (ELEs) group according to the associated stroke-like lesions (SLLs) findings. Clinical characteristics were compared between the SLEs group and the ELEs group among NIID patients and between NIID patients with SLEs and MELAS patients.
    RESULTS: Eleven (47.8%) NIID patients who manifested acute or subacute brain disorders had detectable associated SLLs and were categorized into SLEs group. SLEs patients were more likely to report fever, headache, and seizures instead of sleep disorders than ELEs patients. Four (36.4%) NIID patients with SLEs absence of diagnostic or suggestive NIID imaging features. The clinical manifestations, laboratory test results, and neuroimaging and muscle biopsy histological features of NIID patients with SLEs majorly overlapped with those of late-onset MELAS patients. Older age at the first SLE (OR [95% CI], 1.203 [1.045-1.384]), symptoms of movement disorders on admission (OR [95% CI], 9.625 [1.378-67.246]), and white matter hyperintensity in corpus callosum (OR [95% CI], 16.00 [1.542-166.46]) associated with the NIID diagnosis in patients with SLEs.
    INTERPRETATION: NIID patients with SLEs exhibit evident features of mitochondrial disorders. Interventions aimed at mitochondrial dysfunction might be a promising therapeutic approach for treating this disease.
    DOI:  https://doi.org/10.1002/acn3.52219
  3. Acta Neurol Belg. 2024 Sep 28.
    'The phenotypic conundrum of Trp748Ser variant in POLG gene: a report of two patients'.
    Abhishek Rathore, Gautham Arunachal, Rohan R Mahale, Hansashree Padmanabha, Pooja Mailankody.
      We present two cases of a 23-years and 32-years old female respectively, who presented with recurrent seizures, ataxia, dysarthria, psychomotor slowing. Magnetic resonance imaging (MRI) of the brain in the first patient revealed T2/FLAIR hyperintensity in the bilateral thalamus and cerebellar white matter with diffusion restriction, with no contrast enhancement. In the second patient, magnetic resonance imaging of brain showed FLAIR hyperintensity in precuneus while CSF showed raised HSV IgG titre on first presentation leading to suspicion of infective etiology. The initial differential diagnosis included autoimmune, metabolic and demyelinating causes. However, routine laboratory investigations, cerebrospinal fluid analysis, and autoimmune panel and demyelination workup were inconclusive. Considering the possibility of a genetic-mediated metabolic disorder, genetic testing was carried out leading to the identification of the Trp748Ser variation in POLG gene associated with mitochondrial DNA depletion syndrome. These cases highlight the diagnostic challenges and complexities in identifying rare metabolic encephalopathy, emphasizing the importance of a multidisciplinary approach in such cases.
    Keywords:   POLG variant; Autoimmune encephalopathy; Genetic testing; Metabolic encephalopathy; Mitochondrial DNA depletion syndrome
    DOI:  https://doi.org/10.1007/s13760-024-02640-8
  4. Front Neurol. 2024 ;15 1466275
    Recognizing Leber's Hereditary Optic Neuropathy to avoid delayed diagnosis and misdiagnosis.
    Chiara La Morgia, Maria Lucia Cascavilla, Anna Maria De Negri, Marcello Romano, Fabrizio Canalini, Silvia Rossi, Diego Centonze, Massimo Filippi.
      Leber's Hereditary Optic Neuropathy (LHON) is a maternally inherited optic nerve disease primarily caused by mutations in mitochondrial DNA (mtDNA). The peak of onset is typically between 15 and 30 years, but variability exists. Misdiagnosis, often as inflammatory optic neuritis, delays treatment, compounded by challenges in timely genetic diagnosis. Given the availability of a specific treatment for LHON, its early diagnosis is imperative to ensure therapeutic appropriateness. This work gives an updated guidance about LHON differential diagnosis to clinicians dealing also with multiple sclerosi and neuromyelitis optica spectrtum disorders-related optic neuritis. LHON diagnosis relies on clinical signs and paraclinical evaluations. Differential diagnosis in the acute phase primarily involves distinguishing inflammatory optic neuropathies, considering clinical clues such as ocular pain, fundus appearance and visual recovery. Imaging analysis obtained with Optical Coherence Tomography (OCT) assists clinicians in early recognition of LHON and help avoiding misdiagnosis. Genetic testing for the three most common LHON mutations is recommended initially, followed by comprehensive mtDNA sequencing if suspicion persists despite negative results. We present and discuss crucial strategies for accurate diagnosis and management of LHON cases.
    Keywords:  Leber’s Hereditary Optic Neuropathy; Optical Coherence Tomography; optic nerve; retinal ganglion cell; visual field
    DOI:  https://doi.org/10.3389/fneur.2024.1466275
  5. BMJ Support Palliat Care. 2024 Oct 02. pii: spcare-2024-005135. [Epub ahead of print]
    What do family caregivers of patients with life-threatening diseases need from healthcare professionals? A qualitative study.
    Hinke Elisabeth Hoffstädt, Marcella Cecilia Tam, Arianne Stoppelenburg, Rik Stoevelaar, Leti van Bodegom-Vos, Jenny Theodora van der Steen, Yvette Milene van der Linden, Iris Dewi Hartog.
       OBJECTIVES: To explore the common ground of what family caregivers need in their various roles (caregiver, care recipient and patient's partner, child or friend) from healthcare professionals across healthcare settings and disease trajectories.
    DESIGN: Interviews were conducted with family caregivers of patients with life-threatening diseases who were treated at home, in hospitals, nursing homes or hospices between 2017 and 2022. Reflexive thematic analysis was performed.
    SETTING/PARTICIPANTS: 63 family caregivers of 65 patients were interviewed. Of the patients, 36 (55%) had COVID-19 and 29 (45%) had other life-threatening diseases (eg, advanced cancer, dementia). The majority of family caregivers were women (83%) and children of the patient (56%).
    RESULTS: Three themes were developed regarding family caregivers' core needs across their different roles: (1) 'feeling seen and valued', (2) 'experiencing trust in the provided care' and (3) 'experiencing guidance and security'. Actions of healthcare professionals that meet those needs relate to their contact and relationship with family caregivers, information provision, practical and emotional support, the care for the patient and facilitating the connection between family caregivers and patients.
    DISCUSSION: Healthcare professionals should be trained in meeting family caregivers' core needs, in which their (collaborative) relationship with them plays an important role. Efforts to meet the core needs should be incorporated into healthcare organisations' workflows, and future research should investigate related barriers and facilitators.
    Keywords:  Bereavement; Family management; Palliative Care; Supportive care
    DOI:  https://doi.org/10.1136/spcare-2024-005135
  6. Int J Mol Sci. 2024 Sep 16. pii: 9975. [Epub ahead of print]25(18):
    New Insights into Mitochondria in Health and Diseases.
    Ya Li, Huhu Zhang, Chunjuan Yu, Xiaolei Dong, Fanghao Yang, Mengjun Wang, Ziyuan Wen, Mohan Su, Bing Li, Lina Yang.
      Mitochondria are a unique type of semi-autonomous organelle within the cell that carry out essential functions crucial for the cell's survival and well-being. They are the location where eukaryotic cells carry out energy metabolism. Aside from producing the majority of ATP through oxidative phosphorylation, which provides essential energy for cellular functions, mitochondria also participate in other metabolic processes within the cell, such as the electron transport chain, citric acid cycle, and β-oxidation of fatty acids. Furthermore, mitochondria regulate the production and elimination of ROS, the synthesis of nucleotides and amino acids, the balance of calcium ions, and the process of cell death. Therefore, it is widely accepted that mitochondrial dysfunction is a factor that causes or contributes to the development and advancement of various diseases. These include common systemic diseases, such as aging, diabetes, Parkinson's disease, and cancer, as well as rare metabolic disorders, like Kearns-Sayre syndrome, Leigh disease, and mitochondrial myopathy. This overview outlines the various mechanisms by which mitochondria are involved in numerous illnesses and cellular physiological activities. Additionally, it provides new discoveries regarding the involvement of mitochondria in both disorders and the maintenance of good health.
    Keywords:  ROS; aging; bioenergetics; mitochondrial; mitochondrial dysfunction; mitochondrial targeted therapy; mtDNA; mutations
    DOI:  https://doi.org/10.3390/ijms25189975
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