[MIM 266 150]

(Ataxia with lactic acidosis type 2, Leigh subacute necrosizing encephalopathy by pyruvate carboxylase deficiency, Leigh syndrome by pyruvate carboxylase deficiency)

Incidence: 1/250,000 births. A greater incidence is found in native tribes in Manitoba, Nova Scotia and Saskatchewan. Autosomal recessive transmission or de novo mutation of the PC gene (11q13.4-q13.5) coding for pyruvate carboxylase, a mitochondrial enzyme  converting pyruvate and CO2 into oxaloacetate, a substrate of the Krebs cycle,of neoglucogenesis and aspartate synthesis. (urea cycle). That results in citrate deficiency, hypoglycemia, lactic acidosis due to excess in pyruvate and hyperammoniemia. 

Three clinical pictures have been described:

• infantile form (type A or North American): the carboxylase pyruvate activity is about 2 % of the normal activity; onset in early infancy: growth and psychomotor delay, convulsions, spasticity, ventricular cysts, sometimes Leigh syndrome;  generally severe evolution.
• severe neonatal type (type B or French): total absence of the pyruvate carboxylase activity; lactic acidosis with ketosis, hypoglycemia, hepatomegaly with steatosis and neurological signs (convulsions, coma, muscle tone disorders); very severe evolution with a fatal outcome in the first months of life
• intermittent or benign form (type C): episodes of metabolic acidosis with or without minor neurological signs.

Diagnosis: lactic acidosis that decreases with glucose administration.

Treatment: correct the acute metabolic acidosis; citrate supplements to fuel the Krebs cycle and decrease lactic acidosis; sometimes aspartic acid supplements to improve the functioning of the urea cycle.

Anesthetic implications:

anesthetic management of a mitochondrial cytopathy. Check glycemia, lactates level and ammoniemia. Great sensitivity to the respiratory depressant effects of sedatives.

References : 

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

Updated: November 2020