Beta-ketothiolase (mitochondrial
acetoacetyl-CoA thiolase,
T2) deficiency is a rare
genetic disorder of
ketone utilization and
isoleucine catabolism caused by mutations in the ACAT1 gene. Here we report the first Sri Lankan case of
T2 deficiency confirmed by genetic analysis. A 4-year-old boy presented with the first episode of severe
metabolic ketoacidosis after a febrile illness. On admission, the child was drowsy and had
circulatory collapse needing intubation. Initial investigations were not detective of a cause and symptomatic management did not improve the condition. During the acute episode, his urine organic
acid profile revealed elevations in 3-OH-2-methyl-butyric
acid and
tiglylglycine whilst
2-methylacetoacetic acid was not detected. The differential diagnoses for the urine organic
acid profile included deficiency in T2 or 2-methyl-3-OH-butyryl-CoA
dehydrogenase enzymes. Genetic analysis using polymerase chain reaction and
DNA sequencing of ACAT1 gene revealed that the proband is homozygous for the novel missense likely pathogenic variant c.152C > T p.(Pro51Leu) confirming the diagnosis of
T2 deficiency. This case highlights the importance of suspecting
T2 deficiency in the differential diagnosis of pediatric
metabolic ketoacidosis in preventing life threatening consequences of an otherwise benign disorder.