Molecular epidemiology of phenylalanine hydroxylase deficiency in Southern Italy: a 96% detection rate with ten novel mutations.

Hyperphenylalaninemia (HPA) comprises a group of autosomal recessive disorders mainly caused by phenylalanine hydroxylase (PAH) gene mutations. We investigated PAH mutations in 126 HPA patients from Southern Italy who were identified in a neonatal screening program. The promoter, coding and exon-flanking intronic sequences of the PAH gene were amplified and sequenced. Mutations were identified in 240/249 alleles (detection rate: 96.4%). We found 60 gene variants; the most frequent were p.R261Q (15.7% of alleles), p.A403V (11.6% of alleles) and c.1066-11G > A (8.8% of alleles). The remaining mutations were rare, and ten are novel. This mutation epidemiology differs from that reported for Northern Italy and other European countries. We also identified several discordant genotype/phenotype correlations. About two-thirds of all mild phenylketonuria patients showed at least one tetrahydrobiopterin (BH4)-responsive mutation, and are thus candidates for a customized therapeutic approach.

Growth charts of Down syndrome in Sicily: evaluation of 382 children 0-14 years of age.

We present the results of a study performed on a Sicilian population of children with Down syndrome (DS) 0-14 years of age, observed between 1977 and 1988. Data from the present report concern 382 subjects with nonmosaic 21 trisomy, including 239 males (62.6%) and 143 females (37.4%). We excluded all DS children observed in the same period with associated pathology (congenital heart defects, gastrointestinal malformations, malabsorption, hypothyroidism, and thalassemia). Overall, 1,464 measurements were performed of length or height, weight, and head circumference. Means and standard deviation (SD) were calculated for all of these parameters. Our data confirm a trend toward a progressive improvement of growth in children with DS, as shown in other recent reports. The purpose of this study was also to create a "normal growth pattern" useful to evaluate DS children and also to diagnose early pathologic conditions affecting growth, such as autoimmune diseases.