Introduction: Beta-ketothiolase (mitochondrial acetoacetyl-CoA thiolase, T2) deficiency is a rare inborn error of metabolism affecting isoleucine and ketone metabolism. It typically presents between 6 and 24 months of age with recurrent ketoacidotic episodes triggered by fasting, illness, or infection. We present a case initially suspected to be a toxic ingestion that was ultimately diagnosed as beta-ketothiolase deficiency. Description: A previously healthy 12-month-old male presented with tachypnea, somnolence, and irritability three days after ingesting berries from a backyard “tree of heaven.” He had mild gastrointestinal symptoms following ingestion, then returned to baseline until two days later when parents noted increased clumsiness. The next day he developed rapid breathing and lethargy and was taken to the emergency department. Initial labs revealed a severe metabolic acidosis (pH 7.07, pCO2 11 mmHg, HCO3 3.2 mmol/L, base deficit -24.6, anion gap 30) with normoglycemia (glucose 86 mg/dL), mild hyperammonemia (91 μmol/L), ketonuria, and lactate 1.6 mmol/L. He received fluids, bicarbonate, and was intubated for transport. Workup for ingestion, endocrinopathy, renal tubular acidosis, and infection was unremarkable. Preliminary metabolic workup was non-diagnostic: Urine organic acids analysis, run with 7x dilution due to severe ketosis, failed to detect metabolites consistent with inborn error. Resolution of acidosis and ketosis supported possible environmental etiology, however with severity of presentation, additional workup pursued. Whole genome sequencing identified an ACAT1 mutation suggestive of beta-ketothiolase deficiency. Repeat organic acid testing confirmed the diagnosis, showing elevated 2-methyl-3-hydroxybutyric (2M3HB) and 2-methylacetoacetic (2MAA) levels. Carnitine supplementation was initiated. Due to oral aversion following extubation, an NG was placed for nutritional support. Discussion: Beta-ketothiolase deficiency is exceedingly rare, with fewer than 250 reported cases and diagnosis is often delayed. This case emphasizes the importance of considering metabolic disorders in children with unexplained acidosis and altered mental status, and highlights how severe ketosis may obscure initial organic acid analysis and biochemical diagnosis.
Hadley et al. (Sun,) studied this question.