title: Assessment of the impact of phenylketonuria and its treatment on quality of life of patients and parents from seven European countries.
abstract: BACKGROUND
  The strict and demanding dietary treatment and mild cognitive abnormalities seen in PKU treated from a young age can be expected to affect the health-related quality of life (HRQoL) of patients and their families. Our aim was to describe the HRQoL of patients with PKU from a large international study, using generic HRQoL measures and an innovative PKU-specific HRQoL questionnaire (PKU-QOL). Analyses were exploratory, performed post-hoc on data collected primarily to validate the PKU-QOL.
  
  
  METHODS
  A multicentre, prospective, non-interventional, observational study conducted in France, Germany, Italy, The Netherlands, Spain, Turkey and the UK. Patients diagnosed with PKU aged ≥9 years old and treated with a Phe-restricted diet and/or Phe-free amino acid protein supplements and/or pharmacological therapy were included in the study; parents of at least one patient with PKU aged <18 years were also included. HRQoL was assessed by generic measures (Pediatric Quality-of-Life Inventory; Medical Outcome Survey 36 item Short Form; Child Health Questionnaire 28 item Parent Form) and the newly developed PKU-QOL. Mean generic domain scores were interpreted using published reference values from the general population. PKU-QOL domain scores were described overall and in different subgroups of patients defined according to severity of PKU, overall assessment of patient's health status by the investigator and treatment with tetrahydrobiopterin (BH4).
  
  
  RESULTS
  Data from 559 subjects were analysed: 306 patients (92 children, 110 adolescents, 104 adults) and 253 parents. Mean domain scores of generic measures in the study were comparable to the general population. The highest PKU-QOL impact scores (indicating greater impact) were for emotional impact of PKU, anxiety about blood Phe levels, guilt regarding poor adherence to dietary restrictions or Phe-free amino acid supplement intake and anxiety regarding blood Phe levels during pregnancy. Patients with mild/moderate PKU and those receiving BH4 reported lower practical and emotional impacts of the diet and Phe-free amino acid supplement intake.
  
  
  CONCLUSIONS
  Patients with PKU showed good HRQoL in the study, both with the generic and PKU-specific measures. Negative impacts of PKU on a patient's life, including the emotional impact of PKU and its management, was delineated by the PKU-QOLs across all age groups.
authors.affiliation: Department of Paediatrics, Division of Metabolic Disorders, Academic Medical Centre, University Hospital of Amsterdam, Amsterdam, The Netherlands. a.m.bosch@amc.uva.nl.
authors.forename: Annet M
authors.initials: AM
authors.lastname: Bosch
authors.affiliation: Division of Metabolic Disorders, Department of Paediatrics, University Hospital of Padova, Padova, Italy. alberto.burlina@unipd.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Burlina
authors.affiliation: Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA, USA. acunnin@tulane.edu.
authors.forename: Amy
authors.initials: A
authors.lastname: Cunningham
authors.affiliation: Infection Control Program, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland. Esther.Bettiol@hcuge.ch.
authors.forename: Esther
authors.initials: E
authors.lastname: Bettiol
authors.affiliation: EMD Serono Inc, Billerica, MA, USA. flavie.moreau-stucker@emdserono.com.
authors.forename: Flavie
authors.initials: F
authors.lastname: Moreau-Stucker
authors.affiliation: Mapi, Health Economics & Outcomes Research and Strategic Market Access, Lyon, France.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Koledova
authors.affiliation: Merck KGaA, Darmstadt, Germany. KBenmedjahed@mapigroup.com.
authors.forename: Khadra
authors.initials: K
authors.lastname: Benmedjahed
authors.affiliation: Merck KGaA, Darmstadt, Germany. aregnault@mapigroup.com.
authors.forename: Antoine
authors.initials: A
authors.lastname: Regnault
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001007:Anxiety / Q000209:etiology; D002648:Child; D003072:Cognition Disorders / Q000209:etiology; D004032:Diet; D005060:Europe; D005260:Female; D006305:Health Status Indicators; D006306:Health Surveys / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D010661:Phenylketonurias / Q000178:diet therapy* / Q000523:psychology*; D011446:Prospective Studies; D011788:Quality of Life / Q000523:psychology*; D035583:Rare Diseases / Q000178:diet therapy* / Q000523:psychology*; D011795:Surveys and Questionnaires; D055815:Young Adult