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Miljanić, K.* ; Žigman, T.* ; Tomac, V.* ; Pušeljić, S.* ; Zrno, N.* ; Fumić, K.* ; Ozretić, D.* ; Mayr, J.A.* ; Prokisch, H. ; Barić, I.* ; Petković Ramadža, D.*

Clinical, neuroimaging, genetic, and outcome characteristics of Leigh syndrome: Experience from a single tertiary center.

Paediatr. Croat. 70, 74-85 (2026)
Verlagsversion DOI
Open Access Hybrid
Creative Commons Lizenzvertrag
Aim: Leigh syndrome (LS) is a genetically heterogeneous mitochondrial disorder characterized by subacute necrotizing encephalopathy and early-onset neurological deterioration. We aimed to characterize the clinical presentation, biochemical profile, neuroimaging features, genetic back-ground, and outcomes of children with LS followed at a national tertiary referral center. Methods: We conducted a retrospective cohort study including 17 patients diagnosed with LS between 2012 and 2022. Clinical data, triggering factors, neuroimaging findings, metabolic investigations, genetic results, treatment, and long-term outcomes were systematically extracted from medical records. Results: Median age at onset was 13 months, with 88% presenting before two years of age. Viral infections preceded encephalopathic crises in 41% of patients. All patients demonstrated bilateral symmetrical deep grey matter lesions on brain MRI. Extra-CNS involvement was common, particularly affecting the heart, vision, and hearing. Elevated blood lactate was observed in 88%, and elevated cerebrospinal fluid (CSF) lactate in 85%, including two patients with normal blood lactate but increased CSF concentration, highlighting a potential diagnostic pitfall. Pathogenic variants were identified in 15 patients (8 harbored variants in nuclear DNA and 7 in mitochondrial DNA), while 2 patients remained genetically unresolved. All patients developed permanentneurological sequelae, and 82% became non-ambulatory. Six patients (35%) died, predominantly those with early disease onset and nuclear DNA mutations. Conclusion: LS is associated with substantial morbidity and mortality. Neuroimaging is critical for diagnosis, even when biochemical markers are inconclusive, while CSF lactate assessment may increase diagnostic sensitivity. Early disease onset and nuclear gene mutations were associated with poorer outcomes.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Lactic Acid ; Leigh Disease ; Mitochondrial Diseases ; Neuroimaging
ISSN (print) / ISBN 1330-1403
e-ISSN 1846-405X
Zeitschrift Paediatria Croatica
Quellenangaben Band: 70, Heft: 2, Seiten: 74-85 Artikelnummer: , Supplement: ,
Verlag Children's University Hospital Zagreb
Begutachtungsstatus Peer reviewed
Institut(e) Institiute of Neurogenomics (ING)