title: Clinical profile and molecular characterization of Galactosemia in Brazil: identification of seven novel mutations.
abstract: Classical Galactosemia (CG) is an inborn error of galactose metabolism caused by the deficiency of the galactose-1-phosphate uridyltransferase enzyme. It is transmitted as an autosomal recessive disease and is typically characterized by neonatal galactose intolerance, with complications ranging from neonatal jaundice and liver failure to late complications, such as motor and reproductive dysfunctions. Galactosemia is also heterogeneous from a molecular standpoint, with hundreds of different mutations described in the GALT gene, some of them specific to certain populations, reflecting consequence of founder effect.
  
  
  
  This study reviews the main clinical findings and depicts the spectrum of mutations identified in 19 patients with CG, six with Duarte Galactosemia and one with type 2 Galactosemia in Brazil. Some individuals were diagnosed through expanded newborn screening test, which is not available routinely to all newborns.
  
  
  
  The main classical Galactosemia mutations reported to date were identified in this study, as well as the Duarte variant and seven novel mutations - c.2 T > C (p.M1T), c.97C > A (p.R33S), c.217C > T (p.P73S), c.328 + 1G > A (IVS3 + 1G > A), c.377 + 4A > C (IVS4 + 4A > C), c.287_289delACA (p.N97del) and c.506A > C (p.Q169P). This was expected, given the high miscegenation of the Brazilian population.
  
  
  
  This study expands the mutation spectrum in GALT gene and reinforces the importance of early diagnosis and introduction of dietary treatment, what is possible with the introduction of Galactosemia in neonatal screening programs.
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.|National Institute of Science and Technology in Stem Cell, and Cell Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Garcia
authors.affiliation: Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: José S
authors.initials: JS
authors.lastname: Camelo
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.|National Institute of Science and Technology in Stem Cell, and Cell Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil.|Center for Medical Genomics at Clinical Hospital of the Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Greice A
authors.initials: GA
authors.lastname: Molfetta
authors.affiliation: Department of Neurology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Marlene
authors.initials: M
authors.lastname: Turcato
authors.affiliation: Department of Genetics, Clinical Hospital of the Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Carolina F M
authors.initials: CF
authors.lastname: Souza
authors.affiliation: Department of Pediatrics, Children's Institute, Medical School of the University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Gilda
authors.initials: G
authors.lastname: Porta
authors.affiliation: Department of Medical Genetics, School of Medical Science, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Steiner
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. wilsonjr@usp.br.|National Institute of Science and Technology in Stem Cell, and Cell Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto, SP, Brazil. wilsonjr@usp.br.|Center for Medical Genomics at Clinical Hospital of the Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. wilsonjr@usp.br.
authors.forename: Wilson A
authors.initials: WA
authors.lastname: Silva
mesh_terms: D000483:Alleles; D001483:Base Sequence; D001938:Brazil; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D005693:Galactosemias / Q000235:genetics* / Q000473:pathology*; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation; D011110:Polymorphism, Genetic; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000235:genetics*
chemical_list: D004247:DNA; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase
keywords: GALT; Inborn error of galactose metabolism; Mutation screening