3-oxothiolase activities and [14C]-2-methylbutanoic acid incorporation in cultured fibroblasts from 13 cases of suspected 3-oxothiolase deficiency

Pal Iden, Bruce Middleton, Brian H. Robinson, W. Geoffrey Sherwood, Kenneth M. Gibson, Lawrence Sweetman, Oddmund Søvik

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Cultured fibroblasts from 13 patients with organic aciduria suggesting 3-oxothiolase deficiency were studied by measuring first the capacity of the isoleucine degradative pathways in whole cells, as the incorporation of 1-[14C]-2-methylbutanoic acid into macromolecules, and, second, the activity of 3-oxothiolase in cell homogenates using specific 3-oxoacyl-CoA substrates to identify the different enzymes. Nine patients showed low incorporation by the macromolecular labeling assay, as well as deficiency of 2-methylacetoacetyI-CoA thiolase. In this group of patients, low activity by the macromolecular labeling assay was associated with clinically severe symptoms, and vice versa. Two patients showed reduced macromolecular labeling, but apparently normal 3-oxothiolase. Finally, two patients showed normal activities by either test, the reason for their particular organic aciduria being unknown. In conclusion, occurrence of urinary 2-methyl-3-hydroxybu-tyric acid and/or tiglylglycine is not an unequivocal indicator of the absence of the thiolase that metabolizes 2-methylacetoacetyl-CoA. Measurement of 1-[14C]-2-meth-ylbutanoic acid incorporation in cultured fibroblasts adds important information in studying possible defects of the isoleucine catabolic pathway.

Original languageEnglish (US)
Pages (from-to)518-522
Number of pages5
JournalPediatric Research
Issue number5
StatePublished - Nov 1990
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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