PLASMA ANTIOXIDANT CAPACITY IN 2 CASES OF TYROSINEMIA TYPE-1 - ONE CASE TREATED WITH NTBC

Tyrosinaemia type 1 (TT1) is caused by a deficiency of fumarylacetoacetase, the enzyme that catalyses the last step of the catabolic pathway of tyrosine (Lindblad et al 1977). As a result, the highly reactive compounds maleylacetoacetate (MAA) and fumarylacetoacetate (FAA) are formed, which are thought to be responsible for the severe progressive liver damage and early development of hepatoma seen in this disorder. In rats MAA and FAA have been shown to deplete liver glutathione (Kuhler 1985). In addition, succinylacetone accumulates, which causes a renal Fanconi syndrome and secondary inhibition of porphyrin metabolism, creating risk of neurological crises (Mitchell et al 1990). Treatment consists of restricting dietary tyrosine and methionine, which prevents the renal tubular disease and development of rickets. However, the liver disease is only slowed by dietary therapy and liver transplantation has been necessary to prevent the development of hepatoma. In 1992 Lindstedt et al described the treatment of TT1 by inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC). We describe two similar cases of TT1 born within a year of one another. One patient died just before the publication by Lindstedt, the second was treated with NTBC from 2.3 months of age. The observation that MAA and FAA administration can deplete glutathione, a significant intracellular antioxidant, suggests that a free-radical pathology is implicated in TT1. Plasma total antioxidant activity (TAA) measures the free-radical scavenging activity of plasma against free radicals generated in the aqueous phase. We were interested to see whether plasma TAA was abnormal in TT1 and whether it could be used in monitoring therapy. The method for measuring TAA that was recently described by Miller et al (1993) was used in tandem with other measurements to monitor the treatment of these patients.