bims-tyki2d 2025-12-21 papers

Issue of 2025–12–21
six papers selected by
Zoya Panahloo, UCB

Orphanet J Rare Dis. 2025 Dec 19. 20(1): 623

Comprehensive Iranian guidelines for the diagnosis and management of mitochondrial disorders: an evidence- and consensus-based approach.

Setila Dalili, Noushin Rostampour, Seyedeh Tahereh Mousavi, Saeid Sadeghi Joni, Nejat Mahdieh, Afagh Hassanzadeh Rad, Seyede Tahoura Hakemzadeh, Sara Nikpour, Ali Talea, Hossein Moravvej.

Mitochondrial disorders are a heterogeneous group of inherited metabolic diseases resulting from dysfunctions in oxidative phosphorylation. These conditions predominantly affect high-energy-demand organs such as the brain, heart, liver, and muscles, leading to diverse clinical manifestations and diagnostic challenges. This article presents the first comprehensive Iranian guideline for the diagnosis and management of mitochondrial diseases, developed through an evidence-based and consensus-driven methodology. We conducted a structured literature review across major biomedical databases from 2000 to 2023 and engaged a multidisciplinary panel of Iranian experts to establish context-specific recommendations. The guideline covers clinical presentations, laboratory biomarkers, neuroimaging features, genetic diagnostics, and treatment approaches including "cocktail therapy" and acute management protocols. It also integrates a mitochondrial disease scoring system to standardize diagnosis and provides detailed insights into safe anesthesia practices for affected individuals. Special attention is given to practical implementation in resource-limited settings. These guidelines aim to enhance diagnostic accuracy, optimize management strategies, and improve the quality of life for patients with mitochondrial disorders across Iran and similar healthcare systems.

Keywords: Diagnosis; Genetic testing; Mitochondrial diseases

DOI: https://doi.org/10.1186/s13023-025-04127-y

Pediatr Neurol. 2025 Nov 27. pii: S0887-8994(25)00370-4. [Epub ahead of print]175 223-228

Counseling and Prognostic Challenges in Survivorship and Mortality in Primary Mitochondrial Disease: Reshaping a Once Bleak Landscape.

Ibrahim Elsharkawi, Amy Goldstein, Rebecca D Ganetzky, Eva Morava.

Primary mitochondrial diseases comprise a clinically, genetically, and biochemically heterogenous group of disorders associated with multisystemic involvement and significant morbidity and mortality of various etiologies. To date, no disease modifying therapies have been FDA approved, and treatment is largely symptomatic and supportive. Because of the rarity of mitochondrial specialists, most patients with mitochondrial diseases are cared for by clinicians without mitochondrial-specific expertise. Therefore, these clinicians by necessity rely on existing literature or older prognostic approaches which may be discordant with modern clinical practice and evolving therapeutic strategies and outcomes. Furthermore, existing literature may be skewed to the more severe end of the spectrum as publications may disproportionately focus on the most severe or unusual cases. Prognostic, therapeutic, and palliative discussions should ideally take place in a multidisciplinary setting where shared decision making can take place between the patient, family, and clinician team. Prognosis is increasingly shaped by the unprecedented development of various therapeutic modalities and personalized medicine. We aim to highlight the multipronged challenges and considerations faced in counseling patients and caregivers and draw from our own patient cohorts and observations in contemporary mitochondrial medicine to offer additional insights and future considerations for approaching patient counseling and prognostication.

Keywords: Leigh syndrome; MELAS; Mitochondrial disease prognosis; Mitochondrial dysfunction; Primary mitochondrial disease; Survivorship

DOI: https://doi.org/10.1016/j.pediatrneurol.2025.11.019

Yi Chuan. 2025 Dec;47(12): 1300-1325

Current understanding of mitochondrial DNA genetic diseases and gene therapy.

Cheng Tang, Shun-Qing Xu, Han-Zeng Li.

Mitochondria, as crucial organelles within eukaryotic cells, have their proteins and RNAs encoded by both the nuclear genome and the mitochondrial genome. They play vital roles in energy regulation, cellular metabolism, signal transduction, and various other physiological activities. Additionally, mitochondria interact with multiple organelles to collectively maintain cellular homeostasis. Mitochondria can also be transferred between cells and tissues through mechanisms such as migrasomes. Mitochondrial DNA (mtDNA) mutations often cause severe inherited rare diseases, characterized by tissue specificity, heterogeneity, multiple mutation sites, and challenges in achieving a complete cure. Gene editing of mtDNA holds promise for fundamentally curing such diseases. Traditional gene-editing nucleases, such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nuclease (TALENs), as well as novel gene editors like DddA-derived cytosine base editors (DdCBEs), have been demonstrated to correct certain mtDNA mutations. However, CRISPR-based technologies-despite their superior programmability and efficiency-are currently limited due to the technical bottleneck of inefficient sgRNA delivery into mitochondria. This article systematically reviews the structure and function of mitochondria, related diseases, and the current state of mtDNA gene-editing therapies. Furthermore, it explores future directions for optimizing therapeutic tools to overcome the challenge of sgRNA delivery, thereby addressing the treatment barriers posed by pathogenic mtDNA mutations in inherited rare diseases.

Keywords: CRISPR; mitochondria; mtDNA associated rare diseases; mtDNA editing

DOI: https://doi.org/10.16288/j.yczz.25-032

Obstet Gynecol. 2026 Jan 01. 147(1): e16-e23

Ethical Considerations for Genetic Testing and Counseling in Obstetrics and Gynecology.

Given the increasing availability and complexity of genetic testing, it is imperative that practicing obstetrician-gynecologists and other health care professionals maintain a firm comprehension of the benefits, limitations, and risks of genetic testing offered in their practices. The use of genetic testing has the potential to improve the care of patients and their families; however, the nuances and possible implications of test results can be challenging to interpret and effectively communicate, highlighting the importance of appropriate pretest and posttest counseling as well as expert consultation, when applicable. The challenges for practicing obstetrician-gynecologists often are compounded by severe limitations in time, limited expertise with new testing or rare results, and potentially limited scientific literacy among patients. This document seeks to explore the ethical considerations obstetricians and gynecologists should consider when offering genetic testing in their practices.

DOI: https://doi.org/10.1097/AOG.0000000000006131

J Community Genet. 2025 Dec 16. 17(1): 15

Case-based genomics education and training of neurologists: an Egyptian initiative.

Sherifa Ahmed Hamed, Ali Farrag ElHadad, Mohamad Fawzy.

Many physicians lack confidence in providing genetic services to patients due to a lack of genetic/genomic knowledge. The study aimed to develop and implement a genomic education and training program for neurologists, a real initiative activity. The program consisted of three steps: (1) conducting an exploratory survey to identify knowledge gaps, attitudes, and concerns related to medical genetics/genomics in practical settings. (2) Designing the framework and implementing the national initiative program. (3) Preliminary evaluation of the program outcomes. The program was conducted as part of postgraduate education at a university hospital. Survey responses (42.5%) indicated that many neurologists expressed the importance of genomic medicine but lacked confidence in applying genomic tests in practice and addressing patient questions about genetic diseases. They expressed a preference for face-to-face learning, including case discussions and interpretation of genetic test results. The initiative comprised seven courses conducted over 24 months, with a total of 42 regular meetings. It involved three academic consultant neurologists as expert educators and 45 junior neurologists as trainees. Case discussions and interpretation of authentic genomic results were conducted for 46 patients. Evaluation of the initiative by trainees was promising. Neurologists reported increased genomic knowledge and felt more comfortable referring patients for genetic testing after receiving guidance from expert peers. Findings indicate that neurologists seek scalable and ongoing genomic education and training tailored to their field. Face-to-face, case-based learning led by expert educators in genomics, focusing on neurology, appears to be the most effective approach to address gaps in genomic education and training.

DOI: https://doi.org/10.1007/s12687-025-00836-w