The pathophysiology and treatment of hereditary tyrosinemia type 1

The topic of this review is hepatorenal tyrosinemia (hereditary tyrosinemia type 1 [HT1], or fumarylacetoacetate hydrolase deficiency; OMIM# 276700). HT1 is the most serious and common of the genetic defects in tyrosine degradation. In addition, this disorder has importance as a model of spontaneous self-correction of liver disease, as a model of liver repopulation by transplanted cells and gene therapy, and as a genetic cause of hepatocarcinoma. However, other forms of hypertyrosinemia exist; hence, the differential diagnosis also will be described briefly. Recent years have seen much progress in our understanding of the molecular basis, the pathophysiology, and especially the treatment of HT1. The current intervention with 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3 cyclohexanedione (NTBC) therapy has improved the outcome of this once devastating disorder. The successful repopulation of the HT1 liver with transplanted cells and positive results in the use of gene therapy in animal models may someday lead to therapy in humans that will obviate the need for life-long dietary and pharmacological therapy.