Mitochondrial acetoacetyl-CoA thiolase enzyme deficiency in a 9-month old boy: Atypical urinary metabolic profile with a novel homozygous mutation in ACAT1 gene

[1] Urinary organic acid analysis by gas chromatography-mass spectrometer (GC-MS) typically shows marked excretion of 2-methylacetoacetate, 2-methyl-3-hydroxybutyric acid and tiglylglycine, which are the intermediate metabolites in the isoleucine pathway. [3] Blood and urine amino acid profile by the gas chromatography–mass spectrometry(GC-MS) analysis in our patient was done 2 months after the encephalopathy episode (due to his late referral to our institute), which might have resulted in lack of detection of the typical metabolic profile in him. Since 2-methylacetoacetate is unstable and volatile, it may not be detected in the urine, whereas 2-methyl-3-hydroxybutyric acid and tiglylglycine may not be increased when the patient has mild mutations and when he/she is unstressed. The metabolic profile was also determined when the patient was in a stable phase and without any isoleucine challenge test. [...]assays are not widely available in India, and hence, we considered mutational analysis for confirmation of the diagnosis.