title: [Clinical findings and mutational spectrum in Venezuelan patients with delayed diagnosis of phenylketonuria].
abstract: BACKGROUND
  Massive neonatal screening for phenylketonuria (PKU) began in developed countries in 1963, and eventually disappeared as a cause of mental retardation. Yet, this is not the case in most developing countries.
  
  
  OBJECTIVE
  To describe the phenotype and the genotype of PKU patients with a delayed diagnosis in order to draw attention to the importance of neonatal studies and molecular diagnosis.
  
  
  METHODS
  Clinical data were collected from five unrelated patients by means of a medical assessment. The molecular study was conducted using the DGGE, sequencing and/or restriction analysis techniques to search for mutations in the PAH gene. RESULTS. Owing to the delayed diagnosis all the patients presented severe clinical manifestations, such as psychomotor retardation, atypical behaviours and language disorders. Four of them presented epilepsy and there were two cases of microcephaly. The phenotype was as expected, given the genotype. Seven different mutations were detected in the 10 alleles that were studied. The IVS10nt +5 g>t mutation was the most frequent, followed by the Venezuelan mutation S349L. Furthermore, two patients presented mutated proteins with residual activity, and good results were obtained using BH4 therapy.
  
  
  CONCLUSIONS
  In our country, as in most developing countries, PKU neonatal studies are performed but the programme does not cover the whole neonatal population. In this work, we want to stress the importance of neonatal studies in the welfare of children, as well as the use of molecular diagnosis to improve the therapeutic orientation and genetic counselling of the families involved.
authors.affiliation: Unidad de Estudio de Errores Innatos del Metabolismo, Fundación Instituto de Estudios Avanzados, Laboratorio A Centro de Biociencias y Medicina Molecular, Ctra Nacional Baruta, Venezuela.
authors.forename: A
authors.initials: A
authors.lastname: Mahfoud
authors.forename: M
authors.initials: M
authors.lastname: de Lucca
authors.forename: C L
authors.initials: CL
authors.lastname: Domínguez
authors.forename: I
authors.initials: I
authors.lastname: Arias
authors.forename: L
authors.initials: L
authors.lastname: Casique
authors.forename: K
authors.initials: K
authors.lastname: Araujo
authors.forename: T
authors.initials: T
authors.lastname: Rodríguez
authors.forename: M
authors.initials: M
authors.lastname: Bottaro
authors.forename: A R
authors.initials: AR
authors.lastname: Colmenares
authors.forename: M E
authors.initials: ME
authors.lastname: López
authors.forename: R M
authors.initials: RM
authors.lastname: Merzon
mesh_terms: D002675:Child, Preschool; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010661:Phenylketonurias / Q000175:diagnosis* / Q000235:genetics*; D013997:Time Factors; D014687:Venezuela