Leigh syndrome

Last revised by Dr Rohit Sharma on 06 Oct 2021

Leigh syndrome, also known as subacute necrotizing 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 years, with a presentation in later childhood (juvenile form) or adulthood (adult form) being uncommon. Symptoms include 6,9:

Leigh disease is one of many mitochondrial disorders, due to a broad range of genetic mutations in either nuclear DNA (nDNA) or 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%) and only inherited from the mother 9. Some mutations (e.g. SURF1) 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. 

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.

The factors associated with a worse outcome are 10:

  • disease onset before 6 months of age
  • admission to an intensive care
  • brainstem lesions
  • MRS lactate peak

It is named after Archibald Denis Leigh (1915-1998), a British neuropathologist, who first described the condition in 1951 2,9.

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Cases and figures

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