J. Inher. Metab. Dis. 9 Suppl. 2 (1986)300-302 Short Communication Pyruvate Carboxylase Responsive to Ketosis in a Multiple Carboxylase Deficiency Patient A. VELAZQUEZ 1, D. VON RAESFELD 2, A. GONZALEZ-NORIEGA 1, L. GONZALEZ 1, C. GARAY ~, R. ORTIZ 1 and V. DEE CASTILLO 2. 11nstituto de Investigaciones Biom~dicas, Universidad Nacional Aut6noma de M~xico Apdo. Postal 70228, C.P. 04510 Ciudad Universitaria, D.F., M~xico 2Instituto Nacional de Pediatria, Servicio de Gen~tica Insurgentes Sur 3700-C, 3 ~r piso Col. Insurgentes Cuicuilco CP 04530 MExico, D.F. 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 (Velfizquez 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. CASE HISTORY The patient was a female whose fetal movements were weak and of late onset. There was severe psychomotor and somatic retardation, intractable seizures and spastic paraparesia, but no ketoacidotic episodes. Alanine, pyruvate and lactate were elevated and were further increased after a glucose load. High doses of biotin diminished their blood concentration to the normal range but no clinical improvement was observed. There was also a small urinary excretion of methylci- trate and 3-hydroxypropionate but no metabolites related to 3-methylcrotonyl- CoA carboxylase could be detected. The patient died at 6 years of age: there was severe cerebral atrophy. All three mitochondrial carboxylases were approximately 20% of normal in cultured fibroblasts and increased only 1.5 to 2-fold after growth in medium containing 4000 nmol biotin per litre. When biotin-depleted cells were transferred to a biotin-enriched medium (820 nmol/l), reactivation of the patient's carboxylases was slower for PC than for PCC. Holocarboxylase synthetase activity, using endogenous apoPCC as a substrate, was 15% of the control values; when assayed at varying concentrations of biotin, the Vm~,was decreased but the apparent Km was normal. 300 Journal oflnherited Metabolic Disease. ISSN0141-8955. Copyright© SSIEMand MTP Press Limited, Queen Square, Lancaster, UK. Printed in Great Britain by Titus Wilson & Son Ltd., Kendal.