Pyruvate Carboxylase Responsive to Ketosis in a Multiple Carboxylase Deficiency Patient

Pyruvate carboxylase (PC; EC 6.4.1.1) is a key enzyme for carbohydrate and lipid metabolism. Deficient patients have been described, the deficiency being either isolated (McKusick 26615) or combined with other carboxylase deficiencies (McKusick 25327) (Bartlett et al., 1984). The effects of ketosis are quite different depending on whether it occurs in a normal or in a deficient individual. In the former it is associated with enhanced gluconeogenesis (Newsholme and Leech, 1983); in the latter, ketosis may cause severe acidosis (DeVivo et al., 1977). We have studied a multiple carboxylase deficient (MCD) child with a phenotype resembling PC deficiency (Velazquez et al., in preparation), who did not present an acidotic response to ketosis but instead improved clinically and biochemically when this metabolic state was induced in her.