A Novel Mutation in ACAT1 Causing Beta-Ketothiolase Deficiency in a 4-Year-Old Sri Lankan Boy with Metabolic Ketoacidosis

  • Thivanka Vishwani ManawaduEmail author
  • Eresha Jasinge
  • Meranthi Fernando
  • Pradeep Gamage
  • Anusha Varuni Gunarathne
Case Report


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.


Beta-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.

Compliance with Ethical Standards

Conflict of interest

The authors declare that there is no conflict of interest on the research, authorship, and/or publication of this article.

Informed Consent

Signed informed consent was obtained from the patient’s parents for publication of the manuscript.


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Copyright information

© Association of Clinical Biochemists of India 2019

Authors and Affiliations

  1. 1.Department of BiochemistryMedical Research InstituteColombo 8Sri Lanka
  2. 2.Department of Chemical PathologyLady Ridgeway Hospital for ChildrenColombo 8Sri Lanka
  3. 3.Faculty of MedicineUniversity of KelaniyaKelaniyaSri Lanka
  4. 4.Paediatric Intensive Care UnitTeaching Hospital KarapitiyaGalleSri Lanka

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