[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Conditions](https://durgical.com/en/conditions/) › Leigh syndrome [Conditions](https://durgical.com/en/conditions/) · [Metabolism: mitochondria and energy](https://durgical.com/en/conditions/) # Leigh syndrome Leigh syndrome is a severe childhood mitochondrial disease that damages the basal ganglia and brainstem and makes children lose skills they had learned. Updated 2026-11-01 ## Structures involved Tap one to see what it is and open it in 3D. - [Putamen](https://durgical.com/en/anatomy/putamen/) - [Caudate nucleus](https://durgical.com/en/anatomy/caudate-nucleus/) - [Midbrain](https://durgical.com/en/anatomy/midbrain/) - [Pons](https://durgical.com/en/anatomy/pons/) - [Medulla oblongata](https://durgical.com/en/anatomy/medulla-oblongata/) - [Globus pallidus](https://durgical.com/en/anatomy/globus-pallidus/) - [Substantia nigra](https://durgical.com/en/anatomy/substantia-nigra/) - [Thalamus](https://durgical.com/en/anatomy/thalamus/) - [Cerebellum](https://durgical.com/en/anatomy/anterior-quadrangular-lobule/) ## In biochemistry - [Electron transport chain and oxidative phosphorylation: Step 4 · ATP synthase (complex V)](https://durgical.com/en/biochemistry/pathways/electron-transport-chain-and-oxidative-phosphorylation/#paso-4) - [Complex I (NADH dehydrogenase)](https://durgical.com/en/biochemistry/enzymes/complex-i/) - [Complex III (cytochrome bc₁)](https://durgical.com/en/biochemistry/enzymes/complex-iii/) - [Cytochrome c oxidase (complex IV)](https://durgical.com/en/biochemistry/enzymes/cytochrome-c-oxidase/) - [ATP synthase (complex V)](https://durgical.com/en/biochemistry/enzymes/atp-synthase/) ## In histology - [Organelles: nucleus, ER, Golgi, mitochondria, lysosomes, peroxisomes](https://durgical.com/en/histology/organelles-nucleus-er-golgi-mitochondria-lysosomes-peroxisomes/) ## Why it happens - [Mechanisms of cell injury: ATP, mitochondria, calcium, membranes and DNA](https://durgical.com/en/general-pathology/mechanisms-of-cell-injury-atp-mitochondria-calcium-membranes-and-dna/) - [Nonclassic inheritance: repeat expansions, mitochondrial genes, imprinting, mosaicism](https://durgical.com/en/general-pathology/nonclassic-inheritance-repeat-expansions-mitochondrial-genes-imprinting-mosaicis/) ## What it is Subacute necrotising encephalopathy: symmetrical lesions of the basal ganglia and brainstem from failed energy production, usually starting before age 2. ## Who gets it It affects at least 1 in 40,000 newborns, with much higher rates in some isolated populations. It is the most common presentation of mitochondrial disease in childhood; there are no figures for Colombia. ## Causes - Variants in more than 110 genes, nearly all in oxidative phosphorylation or pyruvate metabolism - Nuclear DNA in about 80%: complex I genes (NDUF), SURF1 (complex IV assembly), PDHA1 (pyruvate dehydrogenase), among others - Mitochondrial DNA in about 20%: for example MT-ATP6 (m.8993T>G) and MT-ND genes ## Risk factors - Consanguinity (autosomal recessive forms) - A mother carrying a mitochondrial DNA variant - Decompensations triggered by infections, fever or fasting ## Pathophysiology Failure of a respiratory complex, ATP synthase or pyruvate dehydrogenase lowers the ATP that neurons and glia need; pyruvate and NADH build up and lactate appears in blood and cerebrospinal fluid. The areas with the highest energy demand (putamen, [caudate nucleus](https://durgical.com/en/anatomy/caudate-nucleus/), brainstem) undergo focal necrosis, gliosis and capillary proliferation, with bilateral symmetrical lesions. Brainstem damage explains the abnormal breathing rhythm and eye movements. ## Symptoms and signs - Loss of motor and language skills already acquired (regression) - Hypotonia, poor sucking and swallowing, vomiting, poor weight gain - Ataxia, dystonia and spasticity - Nystagmus, strabismus, ophthalmoplegia and optic atrophy - Irregular breathing, apneas - Peripheral neuropathy and sometimes cardiomyopathy ## Red flags - Developmental regression after an infection - Apneas or irregular breathing - Lactic acidosis in a hypotonic infant - Symmetrical basal ganglia lesions on MRI ## Diagnosis **Clinical** Developmental regression with basal ganglia and brainstem signs in an infant or young child. **Tests** Lactate and pyruvate in blood and cerebrospinal fluid, amino acids and organic acids; gene panel or exome with mitochondrial DNA analysis; muscle or [skin](https://durgical.com/en/anatomy/skin/) biopsy with respiratory complex assays when genetics is inconclusive. **Imaging** Brain MRI: bilateral symmetrical T2 lesions of the [putamen](https://durgical.com/en/anatomy/putamen/), caudate nuclei and brainstem; spectroscopy shows a lactate peak. ## Treatment **Medical** Early trial of thiamine and biotin: some Leigh-like forms (for example, SLC19A3) respond very well. **Medical** Ketogenic diet in pyruvate dehydrogenase deficiency; coenzyme Q₁₀ in defects of its synthesis. **Acute** Management of decompensations: hydration, correction of acidosis, treatment of infections and respiratory support. **Medical** Avoiding drugs toxic to mitochondria, such as valproate, and prolonged fasting. **Rehabilitation** Physiotherapy, nutritional support (sometimes gastrostomy) and palliative care as needed. ## Complications - Respiratory failure - Aspiration and malnutrition - Epilepsy - Cardiomyopathy - Death in childhood ## Prognosis Almost always progressive; many children die in the first years from respiratory failure. Late-onset forms and treatable ones (thiamine and biotin responsive) do better. ## Test yourself Think of the answer, then tap the question to see it. ## Which brain areas are damaged in Leigh syndrome? The basal ganglia (putamen, caudate) and the brainstem, bilaterally and symmetrically. ## Which complex IV assembly gene is a classic cause of Leigh syndrome? SURF1. ## Why are thiamine and biotin tried in a child with Leigh-like lesions? Some look-alike forms, such as the SLC19A3 transporter defect, respond very well and are treatable. ## About what share of Leigh syndrome cases is due to mitochondrial DNA? About 20%; the rest come from nuclear DNA genes. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/conditions/leigh-syndrome/) ## Related conditions - [MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes)](https://durgical.com/en/conditions/melas/) - [Leber hereditary optic neuropathy (LHON)](https://durgical.com/en/conditions/leber-hereditary-optic-neuropathy/) - [Pyruvate dehydrogenase deficiency](https://durgical.com/en/conditions/pyruvate-dehydrogenase-deficiency/) - [Lactic acidosis](https://durgical.com/en/conditions/lactic-acidosis/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [Leigh syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/leigh-syndrome/) (MedlinePlus, US National Library of Medicine, 2026); [SURF1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/surf1/) (MedlinePlus, US National Library of Medicine, 2026); [MT-ATP6 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/mt-atp6/) (MedlinePlus, US National Library of Medicine, 2026); [Mitochondrial Diseases: MedlinePlus](https://medlineplus.gov/mitochondrialdiseases.html) (MedlinePlus, US National Library of Medicine, 2026). [← All conditions](https://durgical.com/en/conditions/) ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/conditions/leigh-syndrome/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/leigh-syndrome/