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Contributo in rivista
Tipo: Articolo in rivista
Titolo: Clinical and molecular spectra in galactosemic patients from neonatal screening in northeastern Italy: Structural and functional characterization of new variations in the galactose-1-phosphate uridyltransferase (GALT) gene.
Anno di pubblicazione: 2015
Formato: Elettronico Cartaceo
Autori: Viggiano E, Marabotti A, Burlina AP, Cazzorla C, D'Apice MR, Giordano L, Fasan I, Novelli G, Facchiano A, Burlina AB.
Affiliazioni autori: Viggiano E1, Marabotti A2, Burlina AP3, Cazzorla C1, D'Apice MR4, Giordano L1, Fasan I1, Novelli G4, Facchiano A5, Burlina AB6 1Division of Inborn Metabolic Diseases, Department of Paediatrics, University Hospital of Padova, Italy. 2Department of Chemistry and Biology, University of Salerno, via Giovanni Paolo II 132, 84084 Fisciano, SA, Italy. 3Neurological Unit, St. Bassiano Hospital, Bassano del Grappa, Consultant in Neurometabolic Hereditary Diseases at the University Hospital of Padova, Italy. 4Department of Biomedicine and Prevention, School of Medicine, University of Rome "Tor Vergata", Fondazione PTV "Policlinico Tor Vergata", Rome, Italy. 5National Research Council, Institute of Food Science, via Roma 64, 83100 Avellino, Italy. 6Division of Inborn Metabolic Diseases, Department of Paediatrics, University Hospital of Padova, Italy.
Abstract: Classical galactosemia is an autosomal recessive inborn error of metabolism due to mutations of the GALT gene leading to toxic accumulation of galactose and derived metabolites. With the benefit of early diagnosis by neonatal screening and early therapy, the acute presentation of classical galactosemia can be prevented. However, despite early diagnosis and treatment, the long term outcome for these patients is still unpredictable because they may go on to develop cognitive disability, speech problems, neurological and/or movement disorders and, in females, ovarian dysfunction. The objectives of the current study were to report our experience with a group of galactosemic patients identified through the neonatal screening programs in northeastern Italy during the last 30years. No neonatal deaths due to galactosemia complications occurred after the introduction of the neonatal screening program. However, despite the early diagnosis and dietary treatment, the patients with classical galactosemia showed one or more long-term complications. A total of 18 different variations in the GALT gene were found in the patient cohort: 12 missense, 2 frameshift, 1 nonsense, 1 deletion, 1 silent variation, and 1 intronic. Six (p.R33P, p.G83V, p.P244S, p.L267R, p.L267V, p.E271D) were new variations. The most common variation was p.Q188R (12 alleles, 31.5%), followed by p.K285N (6 alleles, 15.7%) and p.N314D (6 alleles, 15.7%). The other variations comprised 1 or 2 alleles. In the patients carrying a new mutation, the biochemical analysis of GALT activity in erythrocytes showed an activity of <1%. In silico analysis (SIFT, PolyPhen-2 and the computational analysis on the static protein structure) showed potentially damaging effects of the six new variations on the GALT protein, thus expanding the genetic spectrum of GALT variations in Italy. The study emphasizes the difficulty in establishing a genotype-phenotype correlation in classical galactosemia and underlines the importance of molecular diagnostic testing prior to making any treatment.
Lingua abstract: inglese medio (1100-1500)
Pagine da: 112
Pagine a: 118
Numero volume: 559
Referee: Sė: Internazionale
Indicizzato da: PubMed 
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