Biochemical investigation of a Brazilian patient with a defect in mitochondrial acetoacetyl‐coenzyme‐A thiolase

Wajner M, Sanseverino MT, Giugliani R, Sweetman L, Yamaguchi S, Fukao T, Shih VE. Biochemical investigation of a Brazilian patient with a defect in mitochondrial acetoacetylcoenzyme‐A thiolase. Clin Genet 1992: 41: 202–205. A case report of 3‐ketothiolase deficiency due to a defect of mitochondrial acetoacetyl‐CoA thiolase protein in a Brazilian boy and its biochemical investigation is presented. The child had moderate generalized hypotonia, EEG alterations and crises of metabolic acidosis following infections. Hypotonia and EEG abnormalities disappeared with a low protein diet, and physical and mental development are normal. Urinary organic acid excretion was typical of 3‐ketothiolase deficiency, showing consistently high levels of 2‐methyl‐3‐hydroxybutyric acid and tiglylglycine. Activation of acetoacetyl‐CoA thiolase activity by potassium (K) ion in cultured fibroblasts was not observed, demonstrating the lack of activity of mitochondrial acetoacetyl‐CoA thiolase. In addition, the signal for the mitochondrial acetoacetyl‐CoA thiolase protein was undetectable in the immunoblot analysis. In the pulse‐chase experiments, the signal for mitochondrial acetoacetyl‐CoA thiolase was detected after a 1‐h pulse but not after a 24‐h chase. These results indicate that the deficiency was caused by an unstable mitochondrial acetoacetyl‐CoA thiolase protein.