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 phenylalanine hydroxylase (PAH) deficiency into regional screening programmes can be supported by the benefit-cost ratio.


METHODS
Tests for the genetic PAH locus were carried out in 151 patients with hyperphenylalaninaemia originally from all of the Italian regions. PAH mutations 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 mutations, 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 provides no advantage, particularly as the correlation between genotype and the metabolic phenotype needed to optimise dietary intervention is still being studied.
Rottoli
A
A
Department of Paediatrics, San Paolo Hospital, Milan, Italy. clinped@mailserver.unimi.it
Gianní
M L
ML
Verduci
E
E
Biondi
M L
ML
Fiori
L
L
Giovannini
M
M
Riva
E
E
D019943:Amino Acid Substitution; D005091:Exons; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D006801:Humans; D007231:Infant, Newborn; D007558:Italy; D009154:Mutation; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000175:diagnosis* / Q000235:genetics*; D017354:Point Mutation; D012680:Sensitivity and Specificity; D017384:Sequence Deletion
D010651:Phenylalanine Hydroxylase