A novel denaturing-HPLC (D-HPLC) procedure for the screening of PAH gene in phenylketonuria.

Capri (NA)

Molecular epidemiology of phenylalanine hydroxilase 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

Risk factors for congenital hypothyroidism: results of a population case-control study (1997-2003).

none26noneMedda E; Olivieri A; Stazi MA; Grandolfo ME; Fazzini C; Baserga M; Burroni M; Cacciari E; Calaciuria F; Cassio A; Chiovato L; Costa P; Leopardi D; Martucci M; Moschini L; Pagliardini S; Parlato G; Pignoro A; Pinchera A; Sala D; Sava L; Stoppioni V; Tancredi F; Valentini F; Vigneri R; Sorcini M;Medda E; Olivieri A; Stazi MA; Grandolfo ME; Fazzini C; Baserga M; Burroni M; Cacciari E; Calaciuria F; Cassio A; Chiovato L; Costa P; Leopardi D; Martucci M; Moschini L; Pagliardini S; Parlato G; Pignoro A; Pinchera A; Sala D; Sava L; Stoppioni V; Tancredi F; Valentini F; Vigneri R; Sorcini M

Risk factors for congenital hypothyroidism: results of a population case-control study

OBJECTIVE: To identify risk factors for permanent and transient congenital hypothyroidism (CH). DESIGN: A population-based case-control study was carried out by using the network created in Italy for the National Register of Infants with CH. METHODS: Four controls were enrolled for each new CH infant; 173 cases and 690 controls were enrolled in 4 years. In order to distinguish among risk factors for permanent and transient CH, diagnosis was re-evaluated 3 years after enrollment when there was a suspicion of transient CH being present. Familial, maternal, neonatal and environmental influences were investigated. RESULTS: An increased risk for permanent CH was detected in twins by a multivariate analysis (odds ratio (OR) = 12.2, 95% confidence interval (CI): 2.4-62.3). A statistically significant association with additional birth defects, female gender and gestational age >40 weeks was also confirmed. Although not significant, an increased risk of CH was observed among infants with a family history of thyroid diseases among parents (OR = 1.9, 95% CI: 0.7-5.2). Maternal diabetes was also found to be slightly associated with permanent CH (OR = 15.7, 95% CI: 0.9-523) in infants who were large for gestational age. With regard to transient CH, intrauterine growth retardation and preterm delivery were independent risk factors for this form of CH. CONCLUSION: This study showed that many risk factors contribute to the aetiology of CH. In particular, our results suggested a multifactorial origin of CH in which genetic and environmental factors play a role in the development of the disease