Leigh syndrome

Leigh syndrome, also known as subacute necrotising encephalomyelopathy (SNEM), is a mitochondrial disorder with progressive neurodegeneration that invariably leads to death, usually in childhood.

Leigh syndrome is encountered in approximately 1 in 40,000 births, although some populations have much higher incidence (e.g. in Quebec, Canada) 9. There is no known gender or racial predilection 9

Typically, symptoms become evident before the age of 2, with the presentation in later childhood (juvenile form) or adulthood (adult form) being uncommon. Symptoms include 6,9:

  • psychomotor delay/regression
  • superimposed signs of basal ganglia and brainstem dysfunction
    • ataxia
    • ophthalmoplegia
    • dystonia 
    • respiratory rhythm disturbance
    • cranial nerve palsies

Leigh disease is one of many mitochondrial disorders, due to a broad range of genetic mutations in both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA)  8,9.

Nuclear DNA mutations are more common (~75%) and are inherited in a Mendelian fashion with both autosomal recessive and X-linked inheritance encountered 9

Cases due to mitochondrial DNA are less common (25%) are therefore only inherited from the mother 9

Some mutations (e.g. SURF 1) are particularly devastating 1

Chronic energy deprivation leads to histological features such as 3:

These findings are similar to those seen in infarction 4.

The inheritance pattern may be either autosomal recessive or X-linked.

CSF lactate may be elevated.

CT demonstrates regions of low-density matching areas of the abnormal T2 signal on MRI (see below) 5. Occasionally some of these areas can show contrast enhancement 5.

MRI abnormalities are heterogeneous and differ depending on the underlying genetic abnormality 8. Generally, the distribution tends to be symmetrical. 

  • T1: usually demonstrates reduced signal in T2 abnormal areas, although some areas of hyperintensity can be seen, as can some enhancement
  • DWI: in the acute setting some restricted diffusion may be evident
  • MR spectroscopy
    • elevated choline
    • occasionally elevated lactate
    • reduced NAA

Prognosis is poor, with death usually occurring in childhood. The later the onset, the slower the deterioration. Death is most frequently due to respiratory failure 6.

It is named after Archibald Denis Leigh, British neuropathologist, who first described the condition in 1951 2,9.

Inborn errors of metabolism
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Article information

rID: 1575
Synonyms or Alternate Spellings:
  • Leigh syndrome
  • Leigh's disease
  • Leighs syndrome
  • Leigh's syndrome
  • Sub acute necrotising encephalomyelopathy
  • Leigh's encephalopathy
  • Subacute Necrotising Encephalomyelopathy (SNEM)
  • Leigh disease

Cases and figures

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    T2- Axial, Symmet...
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