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Leigh syndrome; infantile subacute necrotizing encephalopathy of Leigh
Pathology:
- heterogeneous genetic disorder
- bilaterally symmetrical necrotic lesions in subcortical brain regions, including brainstem, thalamus, basal ganglia, cerebellum, & spinal cord
- the lesions are areas of demyelination, gliosis, necrosis, spongiosis, or capillary proliferation
Genetics:
- deficiency of cytochrome c oxidase
- defects in COX10, COX15
- mutation in 130 kD leucine-rich protein (LRPPRC)
- mutation in gene for MTFMT
- mutation in gene for surfeit-1
- mutations in the mtDNA-encoded ATP6 subunit of ATP synthase
- mutations in X-linked E1-alpha subunit of pyruvate dehydrogenase (PDHA1, PDHE1-A type 1)
- isolated deficiency of mitochondrial complex 1 (NADH:ubiquinone oxidoreductase)
- defects in mitochondrial complex 1 NDUFV1, NDUFS8, & NDUFS4, NDUFS7 MT-ND3, MT-ND5
- defects in mitochondrial complex 2 SDHA
- defects in ATP synthase components MT-ATP6
Clinical manifestations:
- symptoms depend on which areas of the central nervous system are involved
- developmental delay
- weakness
- hypotonia
- clumsiness
- tremor
- ataxia
- Babinski sign
- absent deep tendon reflexes
- blindness
- hyperventilation
- apnea
- dyspnea
- Cheyne-Stokes respirations
- respiratory failure
- hypertrophic cardiomyopathy
- mild facial dysmorphism
Laboratory:
- lactic acid in plasma: lactic_acidosis
- SDHA gene mutation
- PDHA1 gene mutation (X-linked form)
- MTFMT gene mutation
- MT-ATP6 gene mutation
- MT-ND5 gene mutation
- MT-TL1 gene mutation
Complications:
- high mortality due to episodes of severe acidosis & coma
General
genetic syndrome (multisystem disorder)
mitochondrial encephalomyopathy
Database Correlations
OMIM correlations
References
- National Institute of Neurological Disorders and Stroke (NINDS)
NINDS Leigh's Disease Information Page
https://www.ninds.nih.gov/Disorders/All-Disorders/Leighs-Disease-Information-Page