{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:46:25Z","timestamp":1790703985082,"version":"4.1.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The <jats:italic>MRPS36<\/jats:italic> gene encodes the E4 subunit of the 2-oxoglutarate dehydrogenase complex (OGDHC), a critical enzyme in the tricarboxylic acid cycle. OGDHC deficiency can lead to metabolic disorders with a clinical spectrum ranging from fatal neonatal lactic acidosis to variable degrees of global developmental delay and movement disorders. To date, a homozygous <jats:italic>MRPS36<\/jats:italic> variant has been reported as a novel cause of Leigh syndrome in only two siblings, who presented with developmental delay, movement disorders, bilateral striatal necrosis, and reduced OGDHC activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>We report a third case of Leigh syndrome associated with <jats:italic>MRPS36<\/jats:italic> variants in a 2-year-old boy. The patient exhibited with global developmental delay, dystonia, early-onset chorea, and elevated serum lactate levels. Follow-up brain magnetic resonance imaging at 2 years revealed progressive degenerative lesions in the bilateral basal ganglia. Muscle biopsy showed abnormal mitochondrial accumulation beneath the sarcolemma, and the oxygen consumption rate was reduced in skin fibroblasts. Whole-exome sequencing identified two novel compound heterozygous <jats:italic>MRPS36<\/jats:italic> variants: c.42+1G&amp;gt;A (p.?) and c.296G&amp;gt;C (p.Arg99Pro).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This case supports <jats:italic>MRPS36<\/jats:italic> as a novel pathogenic cause of Leigh syndrome, further expanding the genetic spectrum of the disorder. Key clinical features include developmental delay, involuntary movement disorders, progressive basal ganglia atrophy, and a slowly progressive disease course.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2025.1608840","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T05:38:39Z","timestamp":1757655519000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Biallelic variants in MRPS36, encoding a component of the 2-oxoglutarate dehydrogenase complex, cause leigh 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