bims-tyki2d 2025-11-30 papers

Issue of 2025–11–30
four papers selected by
Zoya Panahloo, UCB

Pediatr Nephrol. 2025 Nov 27.

Kidney transplantation in mitochondrial diseases: a systematic review.

Sze Wa Wong, Cheuk Wing Fung, Fred Tomlin, Jelena Stojanovic.

BACKGROUND: Primary mitochondrial diseases are a group of rare, heterogeneous, multisystem disorders. While renal involvement is increasingly recognised, especially in paediatric patients, data on kidney transplantation outcomes in this population remain limited.
OBJECTIVES: To evaluate kidney transplantation outcomes in genetically confirmed primary mitochondrial diseases with multi-organ involvement and provide clinical insights from systematic literature review.
DATA SOURCES: We systematically searched PubMed, MEDLINE, EMBASE and Google Scholar from inception to 10 June 2025 using keywords and MeSH terms related to "mitochondrial disease", "transplantation" and "outcome".
STUDY ELIGIBILITY CRITERIA: We included studies that reported post-transplant clinical outcomes in patients with genetically confirmed primary mitochondrial diseases. Studies without genetic confirmation or transplant follow-up were excluded. Patients with Co-enzyme Q 10 deficiency were excluded as they mainly manifest as isolated steroid resistant nephrotic syndrome with subtypes that respond well to co-enzyme replacement.
PARTICIPANTS AND INTERVENTIONS: Participants included paediatric or adult patients diagnosed with genetically confirmed primary mitochondrial diseases who received isolated kidney transplant from living or deceased donor.
STUDY APPRAISAL AND SYNTHESIS METHODS: Data were extracted on demographics, genotypes, renal and extra-renal features, transplant characteristics, complications and outcomes. Risk of bias was assessed qualitatively by two independent reviewers. Discrepancies were resolved through consensus or discussion with third reviewer. Due to clinical and methodological heterogeneity, a narrative synthesis was performed.
RESULTS: Forty-six patients (15 paediatric, 31 adult) were included from 18 eligible studies. Ten patients had RMND1-related disease. All harboured either homozygous or compound heterozygous c.713A > G variants in RMND1. Thirty patients carried the m.3243A > G mtDNA point mutation variant in MT-TL1. The remaining six patients harboured an m.3271 T > C variant in MT-TL1, single mtDNA deletions, m.8618dup in MT-ATP6, m.12418delA in MT-ATP6 and m.13513G > A in MT-ND5 respectively. At nephrology referral, chronic kidney disease and kidney failure each was present in 26.1% of patients. Median time from renal presentation to kidney failure was 6 years. Graft and patient survival exceeded 90% across different genetic mutations and age groups. Post-transplant deterioration of neurological or metabolic features was reported predominantly in patients with an m.3243A > G variant.
LIMITATIONS: The review is limited by small sample size, selection and reporting bias, heterogeneous follow-up durations and outcome measures. Data were derived mainly from case reports and small case series.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Kidney transplantation is a viable option of kidney replacement therapy for patients with mitochondrial diseases. Patients with primary mitochondrial diseases should be considered for kidney transplantation. Further prospective studies are needed to define optimal transplant timing, immunosuppression strategies and long-term systemic outcomes.
SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD420251086889.

Keywords: Kidney failure kidney transplantation; Patient survival; Primary mitochondrial diseases

DOI: https://doi.org/10.1007/s00467-025-07034-3

bioRxiv. 2025 Nov 11. pii: 2025.11.10.687605. [Epub ahead of print]

Transcriptomic analysis of cells following decreased mitochondrial DNA-copy number reveals compensatory mechanisms in mitochondrial DNA replication and cellular energetics.

Jiaqi Xie, Phyo W Win, Charles Newcomb, Shaopeng Zeng, Christina A Castellani, Dan E Arking.

Mitochondrial DNA copy number (mtDNA-CN) is a metric of mitochondrial function that has been associated with a variety of diseases including cardiovascular disease and all-cause mortality. To investigate genes and pathways affected by mtDNA-CN variation, we perturbed HEK 293T cells with ethidium bromide to deplete mtDNA. Using RNASeq and methylation microarrays, we evaluated transcriptomic and methylomic changes in treated cell lines. We observed an 8-fold decrease in mtDNA-CN and compensatory shifts in mitochondrial transcription to support mtDNA replication. Nuclear transcriptomic and methylomic analysis highlighted changes in metabolic pathways, including oxidative phosphorylation and canonical glycolysis. Longitudinal analyses revealed that the identified genes and pathways have different response timing, with nuclear response lagging behind mitochondrial response. These findings further elucidate the mechanisms behind mtDNA maintenance and responses to cellular energetics as well as mitochondrial-nuclear crosstalk dynamics.

DOI: https://doi.org/10.1101/2025.11.10.687605

J Med Internet Res. 2025 Nov 28. 27 e77087

Social Media Use Among Parents and Caregivers of Children With Rare Genetic Diseases: Scoping Review.

Charlotte Davis, Laura Bogaert, John Powell, Karen Low.

BACKGROUND: Caring for children with rare genetic disorders is challenging due to complex medical needs and limited information. Often, information is scarce due to geographical dispersion and lack of access to expertise. Social media groups are increasingly used in parenting and in healthcare as tools for data sharing and acquisition, and online peer support. Online groups relating to specific rare diseases are increasingly used by parents navigating the difficulties of understanding their child's diagnosis and providing them with support. Parents expect professionals to interact with them about information reported from online groups, but little is known regarding the content within these groups and the impact on families.
OBJECTIVE: We aimed to synthesize current knowledge of social media use among parents and caregivers of children with a rare genetic syndrome to inform how these data might be used in parent-doctor interactions and in the research setting.
METHODS: We completed a comprehensive literature review across Web of Science, PubMed, and PsycINFO using a search strategy with themes of caregivers, rare genetic disease, and social media. Studies published in English from 2005 onwards, with parents and caregivers as a cohort and a focus on rare genetic diseases, were included. In total, 159 articles were identified, which underwent a title sift followed by an abstract sift based on inclusion and exclusion criteria. Reference lists of included articles were also reviewed. A total of 12 studies were included, and a critical synthesis methodology was used to extract relevant points.
RESULTS: Most parents and caregivers use social media platforms, especially Facebook (Meta Platforms, Inc), particularly the group function. They are using social media groups as a tool for finding information related to their child's rare genetic disease. A majority also engaged in online groups by sharing information and contributions of their own. This review highlights that caregivers are seeking three main types of support from social media: (1) medical information around diagnosis and treatments, (2) practical tips on care needs and equipment, and (3) social support, involving connection with other families who shared similar experiences. The use of social media improved accessibility to information regardless of time or geography and reduced feelings of isolation. Caregivers felt empowered in decision-making, and their interactions with health care professionals improved. Challenges include misinformation, concerns around privacy, emotional impacts of comparison, and a lack of online spaces for the rarest conditions.
CONCLUSIONS: Social media is a key tool for caregivers of children with rare genetic diseases. Addressing the associated challenges and harnessing the potential of these platforms can positively impact these families. Health care providers should consider discussing social media engagement in conversations with caregivers, and future research should focus on larger, longitudinal studies to explore the impacts of social media engagement.

Keywords: genetic disease; online support group; parent; rare disease; social media

DOI: https://doi.org/10.2196/77087

JIMD Rep. 2025 Nov;66(6): e70050

Elevated Transaminases: Does It Always Warrant a Liver Biopsy? Lessons Learned From Pompe Disease.

Alicia Khazzeka, Rebecca L Koch, Jeong-A Lim, Jeremy D Ward, Jessica Doxey, William R Jeck, Priya S Kishnani.

Pompe disease (PD) is an autosomal recessive disorder caused by pathogenic variants in GAA, resulting in acid alpha-glucosidase (GAA) deficiency and lysosomal glycogen accumulation. PD is classified into infantile-onset (IOPD), characterized by cardiomyopathy and death within the first year if untreated, and late-onset (LOPD), which presents with gradual muscle weakness at variable ages. Incidentally elevated transaminase levels are common in LOPD and reflect muscle injury rather than liver damage. Creatine kinase (CK) levels are often elevated too, further indicating a myopathic origin. However, these elevated transaminases may be misattributed to liver disease, prompting a liver biopsy. Three charts of patients who underwent liver biopsies prior to a LOPD diagnosis were reviewed, including clinical presentations and diagnostic workups. Liver histology from these biopsies was evaluated and compared to liver pathology in a GAA knockout mouse model. All cases had elevated transaminases and underwent a liver biopsy. One biopsy was normal, while two showed non-specific hepatocyte glycogen accumulation. In all cases, aspartate transaminase (AST) levels were higher than alanine transaminase (ALT) levels and CK levels were elevated. Enzyme testing demonstrated GAA deficiency, and genetic testing identified biallelic variants in GAA, confirming the diagnosis. These cases highlight the importance of meticulous phenotyping before liver biopsy. A muscle origin should be considered when AST:ALT > 1 with elevated CK levels. Neuromuscular gene panels and GAA enzyme testing offer a non-invasive diagnostic approach in LOPD. Notably, even when glycogen accumulation is observed in the liver histologically, liver disease is not associated with PD.

Keywords: GAA enzyme; Pompe disease; creatine kinase; gene sequencing; liver biopsy; transaminases

DOI: https://doi.org/10.1002/jmd2.70050