ArticleMolecular genetics and metabolism2022
Early developmental delay in Leigh syndrome spectrum disorders is associated with poor clinical prognosis.
Article in Molecular genetics and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06843811 (A Pilot Phase 2 Study With Long-Term Extension to Assess the Safety and Efficacy of Sirolimus in Patients With Leigh Syndrome Caused by Genetically-Confirmed Mitochondrial Respiratory Chain Deficiency), which is not on this map. Cited by 9 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Pilot Phase 2 Study With Long-Term Extension to Assess the Safety and Efficacy of Sirolimus in Patients With Leigh Syndrome Caused by Genetically-Confirmed Mitochondrial Respiratory Chain Deficiency
Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- Mitochondria-Targeted Nanotherapies in Aging Neurodegenerative Disorders: Emerging Prospects and Clinical Potential.Advanced healthcare materials · 2026Review
- Linking neurogenesis, oligodendrogenesis, and myelination defects to neurodevelopmental disruption in primary mitochondrial disorders.FEBS letters · 2026Review
- Accelerating Leigh syndrome drug discovery through deep learning screening in brain organoids.Nature communications · 2026Article
- Impaired Complex I dysregulates neural/glial precursors and corpus callosum development revealing postnatal defects in Leigh syndrome mice.EMBO molecular medicine · 2026Article
- Drivers of Diagnostic Delay in Mitochondrial Disease: Missed Recognition of Canonical Features.JIMD reports · 2026Article
- Clinical and Molecular Characterizations of Mitochondrial Disorders: A Tertiary-Care Center Experience.Children (Basel, Switzerland) · 2025Article
- The Clinical Spectrum of Mosaic Genetic Disease.Genes · 2024Review
- Longitudinal natural history studies based on real-world data in rare diseases: Opportunity and a novel approach.Molecular genetics and metabolism · 2024Review
- Expert Panel Curation of 113 Primary Mitochondrial Disease Genes for the Leigh Syndrome Spectrum.Annals of neurology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundLeigh spectrum syndrome (LSS) is a primary mitochondrial disorder characterized by neurodevelopmental regression and metabolic stroke typically in early life. Developmental delay (DD) is known to follow episodes of neurologic regression in LSS, although primary developmental delay (pDD) has been rarely reported. We hypothesized that pDD precedes regression in a broader subset of LSS individuals and may associate with worse long-term educational outcomes.
methodsFrom a retrospective cohort, subjects with pathogenic variant(s) in a nuclear or mitochondrial gene associated with LSS and consistent clinical manifestations and neuroradiological findings. Detailed developmental histories and neurologic outcomes were extracted.
resultsOf 69 LSS subjects, 47 (68.1%) had a history of pDD and 53 (76.8%) had neurodevelopmental regression. We identified 3 distinct developmental phenotypes: [1] pDD followed by regression (N = 31/69, 44.9%), [2] pDD without subsequent regression (16/69, 23.2%), [3] regression without pDD (N = 22/69, 31.9%). A history of pDD was associated with earlier disease onset (p = 0.0003) and worse educational outcomes (OR 22.14).
conclusionLSS is associated with multiple developmental phenotypes and pDD is associated with negative educational outcomes. pDD occurring prior to neurologic regression suggests that mitochondrial energetics impact developmental trajectories prior to acute metabolic failure and regression, providing an opportunity for earlier diagnosis and/or therapeutic intervention.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.