Beta-Ketothiolase Deficiency As A Cause of the "Ketotic Hyperglycinemia Syndrome"

A patient was investigated who had the "ketotic hyperglycinemia syndrome" with normal propionate and methyimalonate metabolism, but with a markedly decreased ability to catabolize isoleucine. Gas liquid chromatography of her urine revealed excretion of large amounts of α-methyl β-hydroxybutyrate and α-methyl-acetoacetate. Thin layer chromatography of dinitrophenylhydrazones of urinary ketones showed large quantities of butanone and smaller amounts of pentanone and hexanone. Incubation of her fibroblasts with isoleucine-u-14C demonstrated the production of butanone-14C. These findings suggest that this child has deficient activity of the β-ketothiolase reaction which cleaves α-methylacetoacetyl CoA to propionyl CoA and acetyl CoA. This child indicates that another potentially treatable disease must be considered in a young infant who presents with vomiting and acidosis.