Inherited metabolic disorder resulting in ketoacidotic
Succinyl-CoA:3-Oxoacid CoA-Transferase (SCOT) Deficiency.
Extremely rare disorder (fewer
than 20 patients described) with autosomal recessive transmission and
chromosomal mapping to 5p13.
SCOT is an extrahepatic, mitochondrial matrix
protein necessary for the synthesis of acetoacetyl-CoA from succinyl-CoA and
acetoacetate. Acetoacetyl-CoA is then cleaved by mitochondrial acetyl-CoA
thiolase and enters the tricarboxylic acid cycle. Of three different
acetyl-CoA thiolases (a peroxisomal, a cytoplasmic, and a mitochondrial
form), only the mitochondrial one needs to be considered here.
usually manifests as a severe ketoacidosis in the first week of life with
tachypnea (caused by severe metabolic acidosis) being the most prominent
sign (later onset has been described). Usually pyruvate, lactate, ammonia,
and blood glucose levels are normal during the ketoacidotic event; however,
hypoglycemia does not rule out SCOT deficiency. Similar to acyl-coenzyme A
cholesterol acyltransferase (ACAT)
deficiency, the treatment of the ketoacidotic attacks consists of
dextrose-containing fluid replacement therapy (keep blood glucose in the
high normal range to suppress ketogenesis) and sodium bicarbonate. Common
triggers of an attack are usually fever and/or infections, and the attacks
tend to present more often with lethargy and coma after the neonatal period.
Between these episodes the patients are free of symptoms, although elevated
concentrations of ketone bodies in the urine can also be found during that
time. Mildly restricted protein and fat intake should help to control
ketogenesis. Some patients are on a carbohydrate-rich diet with oral sodium
Cardiomegaly and congestive heart
failure have been described in some of these patients. The maintenance of high glucose
level is mandatory to prevent ketoacidosis.
Mitochondrial Acetoacetyl-CoA Thiolase
Deficiency (ACAT): Inherited mitochondrial disease affecting isoleucine
catabolism resulting in recurrent episodes of ketoacidosis.
Kassovska-Bratinoba S, Fukao T, Song XQ, et al: Succinyl CoA:3-oxoacid
CoA transferase (SCOT): Human cDNA cloning, human chromosomal mapping to
5p13, and mutation detection in a SCOT-deficient patient. Am J Hum Genet 59:519, 1996.
Synderman SE, Sansaricq C, Middleton B: Succinyl-CoA:3-ketoacid CoA
transferase deficiency. Pediatrics 101:709, 1998.
Tildon JT, Cornblath M: Succinyl-CoA:3-ketoacid CoA transferase deficiency:
A cause for ketoacidosis in infancy. J Clin Invest