Should genetic analysis in newborn screening and a heterozygote test for hyperphenylalaninaemia be recommended? An Italian study

Objective-To determine whether the introduction of genetic analysis for phe nylalanine hydroxylase (PAH) deficiency into regional screening programmes can be supported by the benefit-cost ratio. Method-Tests for the genetic PAH locus were carried out in 151 patients wit h hyperphenylalaninaemia originally from all of the Italian regions. PAH mu tations were identified by extraction of genomic DNA from leucocytes (whole blood in EDTA), PAH exon amplification was determined by polymerase chain reaction, restriction enzyme analysis was carried out for some recognised m utations, and DNA sequence analysis for the other mutations. Results-It was found that the eight most common mutations in the population accounted for 49% of the mutant alleles, which is well below the required standard for effective population screening (90%). Conclusions-Genetic screening for PAH deficiency in Italy does not increase the sensitivity of the methodology and the benefit-cost ratio, and thus pr ovides no advantage, particularly as the correlation between genotype and t he metabolic phenotype needed to optimise dietary intervention is still bei ng studied.