A rare case of β-ketothiolase deficiency presenting as mimicker of diabetic ketoacidosis

Abstract

β-ketothiolase (3-oxothiolase, BKT), also called mitochondrial acetoacetyl-coenzyme-A thiolase (T2), is a mitochondrial enzyme involved in isoleucine catabolism and ketone metabolism. BKT or T2 deficiency is inherited as an autosomal recessive trait and results in a rare inborn error of metabolism called alpha-acetoacetic aciduria. Patients with this disorder usually present with intermittent attacks of ketoacidosis. Here, we report a case of BKT deficiency that mimicked diabetic ketoacidosis (DKA) at presentation and discuss the clinical profile and interpretation of laboratory findings. An 8-month-old male child presented with seizures, coma, hyperglycemia, shock, and high anion gap metabolic acidosis with normal serum lactate and negative urinary ketone requiring correction with sodium bicarbonate, management of shock and sepsis, and mechanical ventilation. During his stay in the hospital, he developed ketonuria and episodes of hypoglycemia on a glucose insulin infusion with persistent metabolic acidosis which prompted us to look for an inborn error of metabolism, as hemoglobin A1C (HbA1C) and C-peptide levels were normal. Both tandem mass spectrometry (TMS) and urinary gas chromatography mass spectrometry (GCMS) were confirmatory. Diagnosis of BKT deficiency was further confirmed with genetic testing which revealed a novel homozygous mutation in the acetyl-CoA acetyltransferase 1 (ACAT1) gene. In infants manifesting with clinical features of diabetic ketoacidosis (DKA), cautious interpretation of laboratory findings and consideration of inborn errors of metabolism including the rare BKT deficiency are needed for a favorable outcome and prediction of prognosis.