Hereditary tyrosinemia type I is a metabolic disorder of autosomal recessive inheritance. The disorder is characterized by progressive liver disease and renal tubular defects with accompanying hypophosphatemic rickets. It occurs in an acute and a chronic form. Hepatocellular carcinoma is frequently encountered in the chronic form of the disorder. The primary enzyme defect is a deficiency of fumarylacetoacetase (FAH) (EC 3.7.1.2), the last enzyme in the degradation of tyrosine. The enzyme defect results in accumulation of fumaryl- and maleyl-acetoacetate which are thought to cause the cellular damage in tyrosinemia. Fumaryl- and maleyl-acetoacetate are reactive compounds and have not been identified in tyrosinemia patients. Succinylacetone, however, presumably derived from these metabolites by reduction and decarboxylation, is elevated in serum and urine from the patients. The diagnosis of tyrosinemia can be established by determination of succinylacetone in urine or serum and by assay of FAH in lymphocytes and fibroblasts. Heterozygotes for FAH can be identified by fumarylacetoacetase analysis in lymphocytes and fibroblasts. Prenatal diagnosis of tyrosinemia is possible by analysis of succinylacetone in amniotic fluid supernatant and by assay of FAH in cultured amniotic fluid cells or chorionic villus material. Genetic variants of FAH may interfere in the prenatal diagnosis of tyrosinemia by the FAH assay and in the detection of the carrier state. Immunoblotting technique has shown absence of immunoreactive protein in liver tissue from tyrosinemia patients. Liver transplantation is as yet the only definite treatment of the disorder.