Neonatal hypoglycaemia in severe succinyl-CoA : 3-oxoacid CoA-transferase deficiency

Succinyl-CoA: 3-oxoacid CoA-transferase (SCOT) deficiency is an inborn erro r of ketone body utilization, characterized by intermittent ketoacidotic cr ises and persistent ketosis. The diagnosis was suspected in a patient who p resented with hypoglycaemia, ketoacidosis band coma at 4 days of age. The h ypoglycaemic tendency was only observed during the first month of life. A n ovel macromolecular labelling assay in cultured skin fibroblasts using D-3- hydroxy[3-C-14]butyrate supported the diagnosis. Subsequently, 9% residual SCOT activity and undetectable cross-reactive protein were noted in fibrobl asts and the patient was found to be homozygous for the G324E SCOT gene mut ation. By 7 years of age, recurrent episodes of ketoacidosis superimposed o n persistent hyperketonaemia had resulted in over 25 hospitalizations requi ring intravenous fluid, glucose and sodium bicarbonate therapy. He has had normal growth but developmental delay and attention deficit-hyperactivity d isorder. A continuous intravenous glucose infusion at 38 mu mol (6.8 mg)/kg per min reduced plasma total ketone levels from greater than 1.5 mmol/L to less than 0.5 mmol/L after 48 h. This indicates that patients with SCOT de ficiency do not always manifest ketosis with administration of a sufficient amount of carbohydrates, but that even under such conditions hyperketonaem ia is difficult to eliminate completely. The presence of hypoglycaemia does not exclude the diagnosis or SCOT deficiency in infancy.