Lactic aciduria

In Leigh s encephalopathy, pyruvate carboxylase is virtually absent from the liver [135, 136]. As a consequence, the concentration of pyruvic acid [137] in the blood rises (up to 5 mg per 100 ml) and this leads to lactic acidaemia [138] (30 mg per 100 ml or more), hypereJaninaemia (up to 12 mg per 100 ml) lactic aciduria and increased excretion of alanine [139], the three substances being interconvertible. 

Congenital lactic acidurias and disorders of pyruvate metabolism... 

Pyruvate may also be converted into alanine by transamination and is reduced by L-lactate dehydrogenase (EC 1.1.1.27) (Holbrook etaL, 1975), the latter reaction providing the basis for the lactic acidosis and lactic aciduria that are observed in primary inherited disorders of pyruvate metabolism and as secondary phenomena in several other metabolic diseases. These latter include... 

Lactic acidosis and lactic aciduria due to uninherited disorders in the newborn and infant... 

Greatly increased lactic aciduria is generally associated with an increased excretion of 2-hydroxy-n-butyric acid (Pettersen et al., 1973 Landaas and Pettersen, 1975) irrespective of the underlying cause of the increased lactate excretion. This acid is thought to arise from 2-oxobutyric acid, a metabolite of methionine, homocystine, cystathionine, serine and threonine, owing to the effect of the changes in NADH/NAD+ ratio in lactic acidosis (Pettersen etaL, 1973). The occurrence of 2-hydroxybutyrate in urine would thus imply an imbalance in cytosolic NADH/NAD and this metabolite may be of value in the further assessment of patients with lactic acidosis. 

Lactic aciduria as a secondary phenomenon in other organic acidurias... 

Rallison, M.L., Meikle, A.W. and Zigrong, W.D. (1979), Hypoglycaemia and lactic aciduria asssociated with fructose-1,6-diphosphatase deficiency. J. Pediatr., 94,933. 

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