Succinyl-CoA:3-Ketoacid CoA-Transferase Deficiency

Inherited metabolic disorder resulting in ketoacidotic episodes.

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.

The disorder 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 bicarbonate supplements.

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.