TYROSINEMIA TYPE-1 AND GLUTATHIONE SYNTHETASE DEFICIENCY - 2 DISORDERS WITH REDUCED HEPATIC THIOL-GROUP CONCENTRATIONS AND A LIVER 4-FUMARYLACETOACETATE HYDROLASE DEFICIENCY

Thiol groups are important components of proteins and their oxidation can lead to a substantial loss of protein function. Patients with two apparently unrelated inborn errors of metabolism, tyrosinaemia type 1 and glutathione synthetase deficiency, have been reported to show redu ced cell glutathione concentrations. We have found that not only gluta thione but also protein thiol concentrations are reduced in the liver in tyrosinaemia type 1 patients. We also report a case of glutathione synthetase deficiency with a substantial deficiency of liver 4-fumaryl acetoacetate hydrolase and provide evidence that glutathione, or some small-molecular-weight thiol, is essential for maintaining stability o f this enzyme in vitro. Our results suggest that the availability of t hiol groups may modify the phenotype of tyrosinaemia type I and that l iver 4-fumarylacetoacetate hydrolase deficiency may be a secondary com plicating factor in some forms of glutathione synthetase deficiency.