Biochemical investigation of a Brazilian patient with a defect in mitochondrial acetoacetylcoenzyme-A thiolase.
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.
Departamento de Bioquimica, Instituto de Biociencias, UFRGS, Porto Alegre, RS, Brasil.
M
M
Wajner
M T
MT
Sanseverino
R
R
Giugliani
L
L
Sweetman
S
S
Yamaguchi
T
T
Fukao
V E
VE
Shih
D000101:Acetyl-CoA C-Acetyltransferase / Q000172:deficiency* / Q000235:genetics; D001938:Brazil; D002675:Child, Preschool; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D011188:Potassium
D000101:Acetyl-CoA C-Acetyltransferase; D011188:Potassium