Severe metabolic acidosis in succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency: case report of a novel pathogenic OXCT1 variant (L131_E132dup) and its pathophysiological basis

Abstract Objectives Ketoacidosis from idiopathic ketotic hypoglycemia (IKH) rarely causes severe acidemia or requires emergency management. We report a rare inborn error of metabolism presenting with severe acidemia secondary to ketoacidosis. Case presentation A 13-month-old boy developed severe respiratory distress during his first febrile episode. Laboratory tests revealed severe anion gap metabolic acidosis (pH 6.866, HCO 3 − 5.6 mmol/L, anion gap 23.4 mEq/L) with markedly elevated D-3-hydroxybutyrate (3HB 6,969 μmol/L). Acidosis improved following blood purification therapy, and he was discharged without sequelae. Metabolic testing suggested a ketone body utilization disorder. He was diagnosed with succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency as a compound heterozygote for a previously reported T435N variant and a novel L131_E132dup variant of OXCT1, with low SCOT activity in lymphocytes. Transient expression analysis of the L131_E132dup cDNA demonstrated no residual enzyme activity. Conclusions We compared data from patients with IKH requiring hospitalization and those with SCOT deficiency. Although 3HB levels did not differ significantly, patients with SCOT deficiency had significantly lower pH and HCO 3 − levels. In ketone body utilization disorders, once ketogenesis is upregulated, ketone bodies rapidly accumulate before renal compensation, leading to severe acidemia. In cases of disproportionate acidemia during ketoacidosis, ketone body utilization disorders should be considered.