A Novel Mutation in ACAT1 Causing Beta-Ketothiolase Deficiency in a 4-Year-Old Sri Lankan Boy with Metabolic Ketoacidosis
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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.
KeywordsBeta-ketothiolase deficiency Metabolic ketoacidosis Urine organic acid ACAT1 Tiglylglycine
We acknowledge Prof. Arndt Rolfs, CEO, Centogene AG, Germany and Prof. Peter Bauer, Chief Scientific Officer, Human Geneticist at Centogene AG, Germany for free of charge genetic analysis.
The authors received no financial support for the research, authorship, and/or publication of this article.
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Conflict of interest
The authors declare that there is no conflict of interest on the research, authorship, and/or publication of this article.
Signed informed consent was obtained from the patient’s parents for publication of the manuscript.
- 5.Hori T, Yamaguchi S, Shinkaku H, Horikawa R, Shigematsu Y, Takayanagi M, et al. Inborn errors of ketone body utilization, c.431A>C (H144P) in ACAT1: subtle abnormality in urinary organic acid analysis and blood acylcarnitine analysis using tandem mass spectrometry. Pediatr Int. 2015;57(1):41–8.CrossRefPubMedGoogle Scholar
- 9.Nguyen KN, Nguyen HT, Can NTB, Do MTT, Bui TP, Fukao T, et al. Beta-ketothiolase deficiency: phenotype, genotype and outcome of 48 Vietnamese patients. Ann Transl Med. 2017;5(Suppl 2):AB014.Google Scholar