Rare Disease Report

New Test to Assess QOL in Patients with PKU

MAY 19, 2015
Lorraine L. Janeczko, MPH

The first set of self-administered online questionnaires designed specifically for patients with phenylketonuria (PKU) and their families to help them assess their condition will soon be available.1
The Phenylketonuria-Quality-of-Life (PKU-QOL) will also be available free to health professionals in individual medical practice and in non-funded academic research later this year through the Mapi Research Trust,2 at the PROQOLID database of testing instruments (www.proqollid.org).3
In an interview with Rare Disease Report, Antione Regnault, PhD, lead study methodologist and research director at Mapi Health Economics & Outcomes Research and Strategic Market Access in Lyon, France, said:
“This instrument was developed, starting in 2007, with and for patients with PKU, so it really reflects their perspective as well as the clinical perspective. It was designed in different versions, adapted to the age of the patient, and was developed in a multinational setting, so should be robust across various cultures.” 
Co-author Annet M. Bosch, MD, PhD, the project’s clinical leader and pediatrician at the University of Amsterdam in the Netherlands, added:
“The PKU-QOL can be a great tool to make sure that the patient perspective is considered when investigating new treatment options. We believe that the PKU-QOL may allow clinicians to monitor the quality of life of their patients and potentially integrate this aspect into their management. We are currently exploring how the PKU-QOL can be efficiently used in this setting.”
“Our results show that, even though a large number of patients with PKU did experience little impact on their lives, there are still some patients whose quality of life, at least some aspects of it, is notably deteriorated.”
“This impact was not largely shown in previous research, in which the quality of life of patients with PKU was frequently shown as comparable to the general population. The existing instruments to measure the impact of PKU were non-specific, so they did not capture the aspects of life that are actually impacted. With the PKU-QOL, we show that for some patients, PKU has a real impact on some aspect of their life, and this should not be overlooked.”

Dr. Renault also noted:
“The PKU-QOL test exists in and has been validated in Dutch, French, German, Italian, and Spanish, Turkish and English, but we would like to see it available in more languages.”
The test is designed to explore patients’ evolving perceptions as they age, help monitor therapy and help understand the impact of the disorder on patients and parents in different cultures.
The PKU-QOL will be available in 7 languages and designed for a different lifespan segment: children age 9 to 11 years (Child PKU-QOL), adolescents 12 to 17 years (Adolescent PKU-QOL), adults age 18 and above (Adult PKU-QOL), and parents of patients (Parent PKU-QOL). The number of items in each version ranges from 40 to 54.
Issues the questionnaires will explore include symptoms and feelings, daily life, dietary protein restriction and phenylalanine-free protein supplements. The tests share similar structure but are adapted to each culture in the seven countries they are designed for. 
After several years of development, the authors1 spent roughly one year analyzing the tests with 306 patients and 253 parents at 34 sites in the Netherlands, France, Germany, Italy, Spain, Turkey and the UK. They found that the measurement properties of the Adolescent, Adult and Parent PKU-QOL questionnaires were overall fairly satisfactory, but were weaker for the Child questionnaire.
The internal consistency reliability of most multi-item scores in adults, adolescents and parents, α >.70, was acceptable, though some scores were not fully satisfactory (the practical impact of PKU: Adolescent, α = .47; Adult, α = .50; as well as the social impact of PKU: Adolescent, α = .45; Adult, α = .63). The reliability coefficients of the Child PKU-QOL scores were low. 1
The analyses of change in Child PKU-QOL scores between baseline and week 2 showed Intraclass Correlation Coefficients (ICC) less than acceptable for most scores (.21–.67); the ICC exceeded the threshold for good test-retest reliability for only Social Impact of PKU (.70), Relationships Within Family Because of Supplements (.72) and Taste – Supplements (.81). 1
The ICC also showed good test-retest reliability for 14 of 31 Adolescent PKU-QOL scores (.70–.95), for 16 of 33 Adult scores (.70–.87) and for 11 of 30 Parent scores (.70–.85). 1

  Other Quality-of-Life Tests

PKU-QOL joins a number of quality-of-life assessment tests that are established but not specific to PKU, including the following:4

  • Pediatric Quality of Life Inventory (PedsQL), which examines physical, emotional, social and school issues;
  • Test of Anxiety and Depression in Infancy and Adolescence (TAD), which investigates symptoms occurring with anxiety and depression;
  • World Health Organization QoL score (WHOQOL-100), which gives adult patients the ability to score their perception of their own quality of life;
  • Beck Depression Inventory (BDI), which evaluates the presence and degree of depression; and the
  • State-Trait Anxiety Inventory form Y (STAI-Y), which examines anxiety level in adults.

About Phenylketonuria

PKU is a rare genetic disorder in which the body can't metabolize phenylalanine from the diet. Phenylalanine is present in many foods, including all proteins and some artificial sweeteners.
If PKU is left untreated, phenylalanine rises to toxic levels in the bloodstream and body, leading to brain damage and intellectual disability, behavioral, heart and other problems.
The disorder is inherited in an autosomal recessive pattern, with both copies of the gene in each cell containing mutations. Each parent of a person with PKU carries one copy of an altered gene as well as a normal gene so shows no signs or symptoms.
Since the 1960s, all babies born in hospitals in the United States are screened for PKU with a heel-prick test that involves taking a few drops of blood to find and treat the problem early. Because of this universal screening, severe PKU is rarely seen.
The best treatment for PKU is a low-protein diet. Newborns with PKU are fed special formulas and older children and adults remain healthy by eating fruits, vegetables, low-protein breads, pastas and cereals, and taking nutritional supplements.
Babies fed the formula soon after birth develop normally and by remaining on their diet regimen for the rest of their lives, they can be symptom-free adults.5,6


1. Regnault A, Burlina A, Cunningham A, et al. Development and psychometric validation of measures to assess the impact of phenylketonuria and its dietary treatment on patients' and parents' quality of life: the phenylketonuria - quality of life (PKU-QOL) questionnaires. Orphanet J Rare Dis 2015;10 (1):59 (http://www.ojrd.com/content/pdf/s13023-015-0261-6.pdf. Published online May 10, 2015.

2. Mapi Research Trust website. http://www.mapi-trust.org. Accessed May 19, 2015.

3. PROQOLID website. http://www.proqolid.org. Accessed May 19, 2015.

4. Chiara Cazzorla, Luca Cegolon, Alessandro P Burlina et al., Quality of Life (QoL) assessment in a cohort of patients with Phenylketonuria. BMC Public Health 2014 14:1243.

5. Learning About Phenylketonuria (PKU). National Human Genome Research Institute website. https://www.genome.gov/25020037 Updated August 21, 2014.

6 What is phenylketonuria? Genetics Home Reference website. http://ghr.nlm.nih.gov/condition/phenylketonuria  Published May 18, 2015.

Image PKU screening procedure courtesy of the US Government and created by Staff Sgt Eric T. Sheler - USAF Photographic Archives.

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