Fumarylacetoacetase measurement as a mass-screening procedure for hereditary tyrosinemia type I

Fluorometric quantitative tyrosine determination on dried-blood spots is the primary neonatal screening test used for tyrosinemia type I (HT) in the province of Quebec. Succinylacetone determination on these same spots is used as the complementary test when the tyrosine level is higher than a given threshold. This procedure has proved to be less discriminant over the past few years because of changes in newborn feeding and because of early discharge of newborns from the nursery. We have developed an enzyme-linked immunosorbent assay (ELISA) to measure the deficient enzyme in HT in dried-blood spots. Fumarylacetoacetase (FAH) (E.C.3.7.1.2) was measured retrospectively by an ELISA on 25 dried-blood samples from proven patients with HT and prospectively in 72,000 specimens received in the neonatal screening program. In this pilot project, FAH was measured first, and, if necessary, succinylacetone was determined as the complementary test. All 25 samples from proven patients and specimens from four other patients detected in the pilot study have shown almost complete absence of FAH in dried-blood samples. At a cutoff level of 12.5% of normal adult blood spotted on the same type of paper, only 30 other cases disclosed FAH levels low enough to warrant succinylacetone measurement but had no detectable succinylacetone. The false-positive rate is thus 1:2,400 with this primary ELISA. However, blood transfusion in newborns prior to blood collection on filter paper may yield false-negative tests, since FAH is present in erythrocytes of normal donors.(ABSTRACT TRUNCATED AT 250 WORDS)