Leigh, disease or syndrome

[MIM 256 000]

(X-linked or infantile subacute necrotizing encephalomyopathy)

Mitochondrial cytopathy consisting of a syndrome with frequent relapses. The onset is often early (< 1 year) and it associates feeding difficulties, ataxia, dystonia and breathing problems (alternance of hyper- and hypoventilation). Typical lesions of the basal ganglia at MRI.


The causes of Leigh syndrome are multiple but all related to a defect in the aerobic energy production:


-        pyruvate-dehydrogenase deficiency  (see this term) one form of which can be aggravated by glucose administration. It causes X-linked subacute necrotizing encephalomyopathy

-        pyruvate-carboxylase deficiency (see this term)

-        respiratory chain dysfunction caused by:


1)        mutations of the complex I genes of mitochondrial origin MTND2, MTND3, MTND5 and MTND6, or of nuclear origin NDUFS1, NDUFS3, NDUFS4, NDUFS7, NDUFS8, NDUFA2, NDUFA9, NDUFA10, NDUFA12, NDUFAF6 and NDUFAF5. A mutation of the MTFMT gene involved in the translation of mitochondrial AND. 

2)        mutations of complex III gene BCS1L (2q35).

3)        mutations of the complex IV genes of mitochondrial MTCO3 or nuclear origin COX10, COX15, SCO2, SURF1, also involved in the  complex IV synthesis, TACO1 and PET100.

4)        mutation of a mitochondrial complex V gene, MTATP6

5)        mutations of the genes coding for the  mitochondrial ARNt proteins: MTTV, MTTK, MTTW, and MTTL1.

6)        mutation in the LRPPRC gene that causes the French Canadian form of Leigh syndrome (Saguenay-Lac-Saint-Jean region) with COX deficiency (MIM 220111).

7)        in addition, coenzyme Q10 deficiency (MIM 607 426) may have the phenotype of Leigh syndrome.


It is estimated that 10-30 % of Leigh syndromes are due to mutations carried by the maternal mitochondrial DNA. This form of the disease is often called MILS (Maternally Inherited Leigh Syndrome).

The genetic cause of a number of Leigh syndromes remains unknown, even in cases where a specific biochemical deficiency has been identified.


Anesthetic implications:

anesthetic management of a mitochondrial cytopathy (see this term). Sometimes: child on a ketogenic diet. Very high sensitivity to the respiratory depressant effects of all sedative agents. Risk of hypothermia.

One study on mouse showed a deleterious effect with halogenated agent (isoflurane).


References : 

-        Shear T, Tobias JD. 
Anesthetic implications of Leigh's syndrome. 
Pediatr Anesth 2004; 14: 792-7. 

-        Dewhirst E, Rehman S, Tobias JD.
Perioperative care of an infant with pyruvate deshydrogenase deficiency.
South Afr J Anaesth Analg 2012 ; 18 :115-8 

-        Spencer KA, Mulholland M, Snell J, Howe M, James K, Hanaford RA, Morgan PG, Sedensky M, Johnson SC.
Volatile anaesthetic toxicity in the genetic mitochondrial disease Leigh syndrome.
Br J Anaesth 2023 ; 131 : 832-46


Updated: November 2023