Evidence for Liver Disease Preceding Amino Acid Abnormalities in Hereditary Tyrosinemia

In hereditary tyrosinemia, an autosomal recessive disorder of infants, it has been postulated that hepatic toxicity arising from defective degradation of tyrosine accounts for the severe liver disease that is a feature of this condition. We measured the concentration of alpha-fetoprotein, a marker for liver disease, and of amino acid in cord blood from three infants with hereditary tyrosinemia and found that the concentration of alpha-fetoprotein was greatly increased at birth, whereas the level of tyrosine was normal or not specifically elevated, and that hypertyrosinemia developed only postnatally. These results indicate that liver disease is prenatal in hereditary tyrosinemia and that therapy aimed at reduction of the elevated tyrosine level is unlikely to be of fundamental value. (N Engl J Med 1983; 308:1265–7.) Hereditary tyrosinemia (tyrosinemia Type I) is an autosomal recessive genetic disorder that produces severe and usually fatal liver disease in infants and children. The cardinal biochemical features are increased levels of tyrosine and methionine in blood and the presence of tyrosine metabolites in urine (tyrosyluria).¹ The liver disease has been attributed to toxicity from defective tyrosine degradation, and on this basis, hereditary tyrosinemia is classified as an inborn error of tyrosine metabolism.² There are reasons to challenge this explanation for the liver injury in hereditary tyrosinemia. A diet that restricts the intake of tyrosine and phenylalanine eliminates the hypertyrosinemia and.