Metabolic acidosis is a key tool in the differentiation of urea cycle defects versus organic acidemias, but it is also quite useful in the evaluation of respiratory or energy transport chain defects. Persistent, severe, metabolic acidosis with absence of urine organic acids will signal primary lactic acidosis. The presence of primary lactic acidosis usually means a defect in pyruvate metabolism (leading to inability to convert lactic acid back to pyruvate to enter the Krebs cycle), gluconeogenesis disorder (leading the body to scavenge pyruvate which is converted to lactic acid with ATP production), respiratory chain defect (causing inability to produce ATP during the Krebs cycle), or a mitochondrial disorder (e.g., error in oxidative phosphorylation). If the metabolic acidosis is due to a primary lactic acidosis, a lactate/pyruvate ratio may be helpful to further narrow the differential diagnosis .
Although it may be possible to determine the general class of metabolic defect, it is often not possible to determine the exact enzyme which is defective or lacking. For example, since there are so many enzymes involved in oxidative phosphorylation, a defect of any one of these will result in a lethal condition.

source= Department of Pediatrics, University of Hawaii John A. Burns School of Medicine