2-methylacetoacetyl-coenzyme A thiolase (beta-ketothiolase) deficiency: one disease - two pathways

Orphanet J Rare Dis. 2020 Apr 28;15(1):106. doi: 10.1186/s13023-020-01357-0.


Background: 2-methylacetoacetyl-coenzyme A thiolase deficiency (MATD; deficiency of mitochondrial acetoacetyl-coenzyme A thiolase T2/ "beta-ketothiolase") is an autosomal recessive disorder of ketone body utilization and isoleucine degradation due to mutations in ACAT1.

Methods: We performed a systematic literature search for all available clinical descriptions of patients with MATD. Two hundred forty-four patients were identified and included in this analysis. Clinical course and biochemical data are presented and discussed.

Results: For 89.6% of patients at least one acute metabolic decompensation was reported. Age at first symptoms ranged from 2 days to 8 years (median 12 months). More than 82% of patients presented in the first 2 years of life, while manifestation in the neonatal period was the exception (3.4%). 77.0% (157 of 204 patients) of patients showed normal psychomotor development without neurologic abnormalities.

Conclusion: This comprehensive data analysis provides a systematic overview on all cases with MATD identified in the literature. It demonstrates that MATD is a rather benign disorder with often favourable outcome, when compared with many other organic acidurias.

Keywords: ACAT1; Beta-ketothiolase; Inborn error of metabolism; Isoleucine; Ketolysis; Ketone body; Metabolic acidosis; Metabolic decompensation; Organic aciduria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA C-Acetyltransferase / genetics
  • Acetyl-CoA C-Acyltransferase* / genetics
  • Acyl Coenzyme A
  • Amino Acid Metabolism, Inborn Errors* / genetics
  • Humans
  • Infant
  • Infant, Newborn


  • Acyl Coenzyme A
  • 2-methylacetoacetyl-coenzyme A
  • Acetyl-CoA C-Acyltransferase
  • Acetyl-CoA C-Acetyltransferase