Leigh syndrome (subacute necrotizing encephalomyelopathy; infantile subacute necrotizing encephalomyelopathy; hyperpyruvicemia with hyper-alpha-alaninemia; gangliosidosis gm2 type 3)

General: Autosomal recessive; metabolic disease occurring in 323j94d infancy and childhood with increased levels of serum lactate, serum pyruvates, blood α-ketoglutarate, and aminoaciduria; course is remittent with early neuro-ophthalmologic manifestations and psychomotor retardation; the later the onset of clinical manifestations, the longer the survival time; acute form in young infants, subacute form in older infants, and chronic course in juveniles; Mutation at nt8993 of mitochondrial DNA has been reported as a common cause of Leigh syndrome; biochemical analysis revealed cytochrome c oxidase deficiency with this condition.

Ocular: Nystagmoid movements or nystagmus; disconjugate ocular movements due to tegmental involvement of brainstem; degrees of visual impairment, depending on pathologic changes involving optic nerves and tracts; optic nerve atrophy; oculomotor palsy; supranuclear gaze palsy; blindness.

Clinical: Spasticity of extremities; ataxia; muscular weakness; hemiparesis; progressive mental deterioration; hearing defects; dysphagia; dyspnea; mild hypotonia; slow development; intermittent abnormal respiratory rhythm; cranial nerve palsies.

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Howard RO, Albert DM. Ocular manifestations of subacute necrotizing encephalomyelopathy (Leigh's disease). Am J Ophthalmol 1972; 74:386.

Kalimo H, et al. Familial subacute necrotizing encephalopathy of the adult form (adult Leigh syndrome). Ann Neurol 1979; 6:200-206.

Leigh D. Subacute necrotizing encephalomyelopathy in an infant. J Neurol Neurosurg Psychiatr 1951; 14:216.

Lombes A, et al. Biochemical and molecular analysis of cytochrome c oxidase deficiency in Leigh's syndrome. Neurology 1991; 41:491-498.

Santorelly FM, et al. The mutation at nt8993 of mitochondrial DNA is a common cause of Leigh's syndrome. Ann Neurol 1993; 34:827-834.

Smith LH. Inherited metabolic disease with pediatric ocular manifestations. In: Albert DM, Jakobiec FA, eds. Principles and Practice of Ophthalmology, vol. IV Philadelphia: WB Saunders, 1994:2777.

Wijburg FA, et al. Leigh syndrome associated with a deficiency of the pyruvate dehydrogenase complex results of treatment with a ketogenic diet. Neuropediatrics 1992; 23: 147-l52.