Biochemical studies in the cerebro-hepato-renal syndrome of Zellweger: a disturbance in the metabolism of pipecolic acid.

The metabolism of pipecolic acid ahs been studied in three patients suffering from the cerebro-hepato-renal syndrome of Zellweger. A marked pipecolic aciduria was observed in these patients and serum levels of pipecolic acid were also elevated. From in vivo studies evidence was obtained that a disturbance in the catabolic pathway of pipecolic acid was present in all patients. This conclusion was based on the delayed return of the serum pipecolic acid concentration to the fasting concentration after oral loading of the patients with DL-pipecolic acid. Moreover, no increase in the excretion of alpha-amino adipic acid was observed in the patients after loading, in contrast with the control subjects, who showed a marked increase in the excretion of this metabolite of pipecolic acid. Further evidence for the presence of a metabolic defect in the catabolism of pipecolic acid was obtained from the observation that patients excreted significantly higher amounts of pipecolic acid during the loading experiment.