Some biochemical observations on biotin deficiency in the rat as a model for human pyruvate carboxylase deficiency

Biotin deficiency was induced in newborn rats by feeding pregnant rats a biotin-deficient, avidin-rich diet. Signs typical of biotin deficiency are seen as soon as the young rat develops its fur. Deficiency of pyruvate carboxylase (PC) activity in the brains of the young animals (70%) is higher than has been reported before. The highest PC activity is found in the brain stem of control and biotin-deficient rats. Normally fed rats show, shortly after birth, a maximum in liver PC activity, which is absent in biotin-deficient animals. The biochemical changes observed in these rats seem to indicate that a specific deficiency of PC activity was induced as exemplified by hyperlactatemia and hypoglycemia and the absence of increased plasma concentrations of propionic acid and beta-methylcrotonic acid. This offers the possibility to use biotin deficiency in the rat as an animal model for patients with lactic acidosis in whom PC deficiency has been postulated.