Unsuccessful attempts to induce peroxisomes in two cases of Zellweger disease by treatment with clofibrate.

The cerebro-hepato-renal syndrome of Zellweger is a fatal hereditary disease and most of the affected infants die before the age of 6 months. Most probably the fatal outcome of the disease is due to an apparent complete lack of peroxisomes in the liver, kidneys, and brain. Treatment with clofibrate is known to increase drastically the number of peroxisomes in mammalian liver. We therefore treated two infants with the Zellweger syndrome with clofibrate (30 and 45 mg/kg body weight, respectively) for 3-4 wk. No clinical effect of the treatment was observed in any of the two cases, and the pattern of abnormal bile acids in serum did not change. No peroxisomes could be detected by electron microscopy of liver biopsies taken immediately after the treatment. Our failure to induce peroxisomes in the two Zellweger patients is in accord with the hypothesis that the protein missing in this autosomal recessive disease is absolutely essential for the formation of peroxisomes.