The pre- and post-natal diagnosis of tyrosinemia type I and the detection of the carrier state by assay of fumarylacetoacetase.

Fumarylacetoacetase has been determined in fibroblasts, lymphocytes and/or liver tissue from 46 patients affected or presumed to be affected with tyrosinemia type I and in fibroblasts or lymphocytes from 80 obligate or presumed obligate heterozygotes. Eleven patients did not have deficient enzyme activity and 11 parents did not have intermediate enzyme activities compatible with heterozygosity for tyrosinemia. In altogether 15 of the 51 families investigated the fumarylacetoacetase activity of the patient and/or the parents was not compatible with tyrosinemia in the family. Prenatal determination of fumarylacetoacetase, in cultured amniotic fluid cells or chorionic villus material, has been performed in 24 pregnancies at risk or presumed to be at risk for a child with tyrosinemia. In six cases the enzyme activity was deficient, consistent with an affected foetus. Elevation of succinylacetone was found in 32 of the 35 patients with fumarylacetoacetase deficiency when the enzyme assay was carried out. In two cases with deficient fumarylacetoacetase activity, succinylacetone was searched for but had not been found to be elevated when the enzyme defect was demonstrated. Succinylacetone, if searched for, was not elevated in any of the cases with normal fumarylacetoacetase activity.