title: Manifestations and evolution of Wilson disease in pediatric patients carrying ATP7B mutation L708P.
abstract: OBJECTIVE
  The aim of the study was to characterize a group of 11 pediatric patients, ages 3 to 13 years, affected by Wilson disease (WD) in the island of Gran Canaria, Spain.
  
  
  METHODS
  Genetic, biochemical, and pathological features, together with their response to treatment and clinical evolution, have been analyzed for this group of patients.
  
  
  RESULTS
  Genetically, the group was rather homogeneous, with an extremely high prevalence of the L708P mutation (4 homozygotes and 5 heterozygotes). Despite being initially screened because of asymptomatic hypertransaminemia, all of the patients presented with some degree of liver damage that was never accompanied by any neurological manifestation. Hepatic damage was most severe in a compound heterozygote with a novel mutation, G1266W, affecting a motif in the ATP7B polypeptide that is greatly conserved in similar proteins among metazoans. Ceruloplasmin and copper serum levels, together with the determination of hepatic copper content, were found to be of great diagnostic value, whereas urine copper measurements were found to be much less conclusive. All of the patients responded well to treatment with D-penicillamine with no documented adverse reactions.
  
  
  CONCLUSIONS
  The patients in Gran Canaria constitute, overall, one of the largest groups of patients with WD with a high incidence of a single mutation, allowing us to define the early clinical symptoms and the evolution of the disease in patients carrying the ATP7B L708P mutant allele, and the study of WD in a genetically homogeneous background.
authors.affiliation: Departamento de Ciencias Clínicas, Universidad de Las Palmas de Gran Canaria, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Peña-Quintana
authors.forename: María R
authors.initials: MR
authors.lastname: García-Luzardo
authors.forename: Luis
authors.initials: L
authors.lastname: García-Villarreal
authors.forename: María D
authors.initials: MD
authors.lastname: Arias-Santos
authors.forename: Paloma
authors.initials: P
authors.lastname: Garay-Sánchez
authors.forename: Alfredo
authors.initials: A
authors.lastname: Santana
authors.forename: Daniel
authors.initials: D
authors.lastname: González-Santana
authors.forename: Juan C
authors.initials: JC
authors.lastname: Ramos-Varela
authors.forename: Ramiro
authors.initials: R
authors.lastname: Rial-González
authors.forename: Antonio
authors.initials: A
authors.lastname: Tugores
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D027682:Cation Transport Proteins / Q000235:genetics*; D002570:Ceruloplasmin / Q000378:metabolism; D002614:Chelating Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009154:Mutation; D010396:Penicillamine / Q000627:therapeutic use
chemical_list: D027682:Cation Transport Proteins; D002614:Chelating Agents; D003300:Copper; D002570:Ceruloplasmin; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; D010396:Penicillamine