| Item type | Value | Notes | Source (with PMID if available) | URL | Publication date |
|---|---|---|---|---|---|
| Identifier | Leigh syndrome (OMIM 256000) | Baldo & Vilarinho review explicitly states “Leigh Syndrome (OMIM 256000)”; classic synonym is subacute necrotizing encephalomyelopathy (pqac-00000000, pqac-00000017) | Baldo MS, Vilarinho L. *Orphanet J Rare Dis.* 2020; PMID not provided in gathered context | https://doi.org/10.1186/s13023-020-1297-9 | 2020-01 |
| Synonym | Subacute necrotizing encephalomyelopathy | Classical neuropathologic designation used for LS/LSS in reviews and ClinGen-oriented literature (pqac-00000000, pqac-00000011) | Lake NJ et al. *Ann Neurol.* 2016; PMID not provided in gathered context | https://doi.org/10.1002/ana.24551 | 2016-02 |
| Synonym | Leigh syndrome spectrum (LSS) | Newer umbrella term encompassing classical Leigh syndrome and Leigh-like phenotypes; used in recent diagnostic and ClinGen frameworks (pqac-00000001, pqac-00000011) | Baldo MS et al. *Diagnostics.* 2024; PMID not provided in gathered context | https://doi.org/10.3390/diagnostics14192133 | 2024-09 |
| Identifier/Nomenclature | ClinGen Mito GCEP curated 113 primary mitochondrial disease genes for LSS | Expert-panel framework to standardize LSS definition and gene–disease relationships; 114 GDRs assessed (31 definitive, 38 moderate, 43 limited, 2 disputed) (pqac-00000011, pqac-00000013) | McCormick E et al. *Ann Neurol.* 2023; PMID not provided in gathered context | https://doi.org/10.1002/ana.26716 | 2023-08 |
| Epidemiology | Prevalence/birth prevalence ~1 per 40,000 live births | Repeated across authoritative reviews and recent diagnostic review as the standard headline prevalence estimate (pqac-00000000, pqac-00000001, pqac-00000007) | Lake NJ et al. *Ann Neurol.* 2016; PMID not provided in gathered context | https://doi.org/10.1002/ana.24551 | 2016-02 |
| Epidemiology | Higher-prevalence founder populations reported | Examples include LRPPRC in Saguenay–Lac-Saint-Jean (~1:2000) and SUCLA2 in the Faroe Islands (~1:1700) (pqac-00000007) | Lim AZ. Natural history thesis/report, 2022; PMID not provided in gathered context | Not available in gathered context | 2022 |
| Epidemiology | Most common pediatric manifestation of primary mitochondrial disease | Leigh syndrome/LSS is consistently described as the most frequent pediatric mitochondrial neurodegenerative disorder (pqac-00000001, pqac-00000011) | Baldo MS et al. *Diagnostics.* 2024; PMID not provided in gathered context | https://doi.org/10.3390/diagnostics14192133 | 2024-09 |
| Prognosis | Typical onset before age 2 years | Onset generally by age 2 years; median age at onset 9 months in one natural-history cohort (pqac-00000000, pqac-00000004) | Lim AZ et al. *Ann Neurol.* 2022; PMID not provided in gathered context | https://doi.org/10.1002/ana.26260 | 2022-11 |
| Prognosis | Often rapidly progressive | Authoritative review notes progression is often rapid, with classic severe pediatric course (pqac-00000000) | Lake NJ et al. *Ann Neurol.* 2016; PMID not provided in gathered context | https://doi.org/10.1002/ana.24551 | 2016-02 |
| Prognosis | Typical historical outcome: death by ~3 years in severe early-onset disease | Review summarizes classic expectation of death by age 3; more recent cohorts show genotype-specific variability and some longer survival (pqac-00000000, pqac-00000003) | Lake NJ et al. *Ann Neurol.* 2016; PMID not provided in gathered context | https://doi.org/10.1002/ana.24551 | 2016-02 |
| Prognosis | Nearly 90% of deaths occurred by age 6 in a Japanese cohort | In 166 patients, early onset (<6 months) strongly worsened mortality; all neonatal-onset patients were deceased or bedridden (pqac-00000004) | Ogawa E et al. *J Inherit Metab Dis.* 2020; PMID not provided in gathered context | https://doi.org/10.1002/jimd.12218 | 2020-02 |
| Prognosis | Genotype-specific 3-year survival differs substantially | Poorest outcomes (≤50% 3-year survival) reported for MT-ND5, MT-ATP6 m.8993T>C/m.9176T>C, SURF1, ALDH5A1; treatable causes such as ECHS1 and SLC19A3 had 100% 3-year survival in the Beijing cohort (pqac-00000003) | Stenton SL et al. *Ann Neurol.* 2022; PMID not provided in gathered context | https://doi.org/10.1002/ana.26313 | 2022-03 |
| Prognosis | Registry snapshot suggests substantial burden but some resilience | Global registry (n=116) found high disease burden, relatively short time to diagnosis, generally good reported QoL, and caregivers reporting significant stress; ~70% lived outside the US (pqac-00000014, pqac-00000015, pqac-00000017) | Zilber S et al. *Orphanet J Rare Dis.* 2023; PMID not provided in gathered context | https://doi.org/10.1186/s13023-023-02886-0 | 2023-09 |


*Table: This table summarizes core nomenclature, identifiers, and headline epidemiology/prognosis facts for Leigh syndrome/Leigh syndrome spectrum using only gathered evidence. It is useful as a compact reference for disease knowledge base population.*