Biochemical investigations on a patient with a defect in cytosolic acetoacetyl‐CoA thiolase, associated with mental retardation

Abstract

A severely mentally retarded boy with two normal siblings was persistently found to excrete elevated amounts of 3-hydroxybutyrate and acetoacetate. Enzyme analysis in cultured fibroblasts revealed a probable deficiency in cytosolic acetoacetyl-CoA thiolase which was about half the control activity with normal mitochondrial thiolase activities. Treatment with reduced dietary fat was initiated and a rapid reduction of the ketosis to biochemical normality was demonstrated. Shortly after initiating dietary treatment he presented with severe gastrointestinal problems and the histological features of colitis cystica superficialis. This appeared to respond to intravenous hydrocortisone therapy with an apparent complete recovery.

Progressive Infantile Neurodegeneration Caused by 2-Methyl-3-Hydroxybutyryl-CoA Dehydrogenase Deficiency: A Novel Inborn Error of Branched-Chain Fatty Acid and Isoleucine Metabolism

“…It is possible that in nervous tissue, 2-methyl-3-ketoacyl-CoA esters that accumulate in 3-ketothiolase deficiency are sufficiently metabolized by one of the other thiolases (4) and that the urinary metabolite pattern does not exactly reflect the metabolic situation in the brain. Interestingly, a neurodegenerative disease with a course somewhat similar to that observed in our patient has been described in cytosolic acetoacetyl-CoA thiolase deficiency (5,6). One of the two patients reported developed normally in the first months of life but subsequently started to lose acquired motor skills and showed ataxic and choreatiform movements; blood lactate was consistently elevated.…”

Molecular basis of zellweger syndrome,β-ketothiolase deficiency and mucopolysaccharidoses

“…Deficiencies of other thiolases have also been reported and symptoms differ from those related to T2 deficiency (CT: De Groot et al, 1977;Bennett et al, 1984;PT: Schram et al, 1987;TFP: Wanders et al, 1992), although gene mutations in these deficiencies have not been detected. Therefore, the term "fl-ketothiolase deficiency" seems imprecise when referring to T2 deficiency alone.…”

Molecular cloning and sequence of the complementary DNA encoding human mitochondrial acetoacetyl-coenzyme A thiolase and study of the variant enzymes in cultured fibroblasts from patients with 3-ketothiolase deficiency.

“…T2 alone seems to be responsible for the cleavage of 2-methylacetoacetyl-CoA, an intermediate of isoleucine catabolism (7,16). The term "3KTD" is commonly used for T2 deficiency, although deficiencies of PT and CT have also been reported (17,18).…”