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

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.