European Journal of Pediatrics

, Volume 139, Issue 1, pp 39–42 | Cite as

Beta-ketothiolase deficiency in a family confirmed by in vitro enzymatic assays in fibroblasts

  • R. B. H. Schutgens
  • B. Middleton
  • J. F. v. d. Blij
  • J. W. E. Oorthuys
  • H. A. Veder
  • T. Vulsma
  • W. H. H. Tegelaers
Original Investigations


A boy of 6.5 years and his 36-year-old father were found to excrete elevated amounts of urinary 2-methyl-3-hydroxybutyric acid and tiglylglycine, as is found in patients with a presumed β-ketothiolase deficiency. Psychomotor development of both patients was normal. The clinical picture was mild, as only during periods with infections does metabolic acidosis develop and clinical abnormalities become noticeable. In vivo loading tests with protein and especially with L(+) isoleucine resulted in massive excretion of 2-methyl-3-hydroxy-butyric acid and tiglyglycine. Enzymatic activity of 3-keto-acyl-CoA thiolase was not detectable in patients fibroblasts using 2-methyl-acetoacetyl-CoA as substrate, whereas with acetoacetyl-CoA as substrate, a lowered activity was found. As ketogenesis in these patients was normal, these findings strongly suggest that the inborn metabolic defect known as β-ketothiolase deficiency is caused by a deficiency of the mitochondrial acetoacyl-CoA specific thiolase isoenzyme involved in thiolysis of (2-methyl) acetoacetyl-CoA, whereas the isoenzyme involved in ketogenesis is not affected.

Key words

Beta-ketothiolase deficiency 2-methyl-3-hydroxybutyric aciduria 2-Methyl-acetoacetyl-coenzyme-A-thiolase deficiency Organic aciduria 


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Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • R. B. H. Schutgens
    • 1
  • B. Middleton
    • 2
  • J. F. v. d. Blij
    • 3
  • J. W. E. Oorthuys
    • 1
  • H. A. Veder
    • 1
  • T. Vulsma
    • 1
  • W. H. H. Tegelaers
    • 1
  1. 1.Department of PediatricsUniversity Hospital AmsterdamAmsterdamThe Netherlands
  2. 2.Department of BiochemistryThe University of Nottingham Medical SchoolNottinghamUK
  3. 3.Medical Centre AlkmaarAlkmaarThe Netherlands

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