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Linguistic Validation of the Phenylketonuria - Quality of Life (PKU-QOL) Questionnaire Into Brazilian Portuguese

Abstract

The phenylketonuria - quality of life (PKU-QOL) questionnaire was developed to assess the impact of phenylketonuria (PKU) and its treatment on the health-related quality of life (HRQL) of patients and their caregivers. Available in four versions (child, adolescent, adult and parent), it was developed and validated in eight countries. The objective of this study was to linguistically validate the PKU-QOL questionnaire in Brazilian Portuguese for use in Brazil by clinicians who take care of PKU patients. The translation method used a standard linguistic validation process. The British English version served as a basis for translation. No major cultural or semantic issues were found during the process. The main difficulty was the use of the acronym “PKU” in the first translations. During the cognitive interviews, respondents made the confusion between the disease itself and the food supplement since it is written “PKU” or “COMIDA-PKU” on the packaging of the product. To overcome this issue, it was decided to use fenilcetonuria (fenil) or fenil alone throughout all versions. The PKU-QOL will be valuable for Brazilian healthcare providers in individualizing treatment and managing patients with PKU.

Keywords
phenylketonuria; PKU-QOL questionnaire; health-related quality of life; Translation; linguistic validation; cross-cultural

Introduction

Phenylketonuria (PKU), or phenylalanine hydroxylase deficiency, is a rare autosomal recessive disease, triggered by the deficiency of the hepatic enzyme, phenylalanine hydroxylase (PAH) that oxidizes the essential amino acid phenylalanine (PHE) in tyrosine (TYR) [11. Blau N, van Spronsen FJ, Levy HL. Phenylketonuria. Lancet. 2010;376(9750):1417-1427. https://doi.org/10.1016/S0140-6736(10)60961-0 .
https://doi.org/10.1016/S0140-6736(10)60...
]. This error causes increased PHE blood concentrations and leads to a toxic accumulation in the brain, resulting in cognitive deficiencies, emotional disturbance and psychosocial disabilities [11. Blau N, van Spronsen FJ, Levy HL. Phenylketonuria. Lancet. 2010;376(9750):1417-1427. https://doi.org/10.1016/S0140-6736(10)60961-0 .
https://doi.org/10.1016/S0140-6736(10)60...
, 22. Waisbren SE, Noel K, Fahrbach K, et al. Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis. Mol Genet Metab. 2007;92(1-2):63-70. https://doi.org/10.1016/j.ymgme.2007.05.006 PMID:17591452 .
https://doi.org/10.1016/j.ymgme.2007.05....
].

Current treatment for PKU involves life-long dietary restrictions in PHE excluding most protein-containing foods. Medical foods are an essential component of this diet [33. Vockley J, Andersson HC, Antshel KM, et al. American College of Medical Genetics and Genomics Therapeutics Committee. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med. 2014;16(2):188-200. https://doi.org/10.1038/gim.2013.157 .
https://doi.org/10.1038/gim.2013.157 ...
] with the goal of maintaining blood PHE in the range of 120-360 μmol/l [33. Vockley J, Andersson HC, Antshel KM, et al. American College of Medical Genetics and Genomics Therapeutics Committee. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med. 2014;16(2):188-200. https://doi.org/10.1038/gim.2013.157 .
https://doi.org/10.1038/gim.2013.157 ...
]. Medical foods for PKU include essential TYR and varying quantities of carbohydrate, fat, vitamins, and minerals, and provide the amino acids needed for normal growth and development [44. Camp KM, Lloyd-Puryear MA, Huntington KL. Nutritional treatment for inborn errors of metabolism: indications, regulations, and availability of medical foods and dietary supplements using phenylketonuria as an example. Mol Genet Metab. 2012;107(1-2):3-9. https://doi.org/10.1016/j.ymgme.2012.07.005 .
https://doi.org/10.1016/j.ymgme.2012.07....
, 55. Singh RH, Rohr F, Frazier D, et al. Recommendations for the nutrition management of phenylalanine hydroxylase deficiency. Genet Med. 2014;16(2):121-131. https://doi.org/10.1038/gim.2013.179 PMID:24385075 .
https://doi.org/10.1038/gim.2013.179...
]. The only approved medicinal product for PKU, in Canada, Brazil, Japan, the European Union, and the USA, is sapropterin dihydrochloride.

Even treated, PKU patients may experience psychological and neurocognitive problems [66. Giovannini M, Verduci E, Salvatici E, Paci S, Riva E. Phenylketonuria: nutritional advances and challenges. Nutr Metab Lond. 2012;9(1):7. https://doi.org/10.1186/1743-7075-9-7 .
https://doi.org/10.1186/1743-7075-9-7 ...
]. In a systematic literature review, Enns et al. reported [77. Enns GM, Koch R, Brumm V, Blakely E, Suter R, Jurecki E. Suboptimal outcomes in patients with PKU treated early with diet alone: revisiting the evidence. Mol Genet Metab. 2010;101(2-3):99-109. https://doi.org/10.1016/j.ymgme.2010.05.017 .
https://doi.org/10.1016/j.ymgme.2010.05....
] that overall intellectual functioning and specific neuropsychological abilities may be suboptimal in patients having either high or fluctuating blood PHE concentrations and treated with diet only. Executive dysfunction in working memory, mental flexibility, organizational strategy and conceptual reasoning were accounted. They also described attentional problems leading to negative impacts on academic progress, as well as on self-esteem and emotional development. Regarding the assessment of health-related quality of life (HRQL) outcomes, the same authors [77. Enns GM, Koch R, Brumm V, Blakely E, Suter R, Jurecki E. Suboptimal outcomes in patients with PKU treated early with diet alone: revisiting the evidence. Mol Genet Metab. 2010;101(2-3):99-109. https://doi.org/10.1016/j.ymgme.2010.05.017 .
https://doi.org/10.1016/j.ymgme.2010.05....
] reported contrasting results. Six studies were reviewed: two of them described optimal outcomes, i.e. HRQL comparable to normal controls [88. Bosch AM, Tybout W, van Spronsen FJ, de Valk HW, Wijburg FA, Grootenhuis MA. The course of life and quality of life of early and continuously treated Dutch patients with phenylketonuria. J. Inherit. Metab. Dis. 2007;30(1):29-34. https://doi.org/10.1007/s10545-006-0433-6 .
https://doi.org/10.1007/s10545-006-0433-...
, 99. Bosch AM, Maurice-Stam H, Wijburg FA, Grootenhuis MA. Remarkable differences: the course of life of young adults with galactosaemia and PKU. J. Inherit. Metab. Dis. 2009;32(6):706-712. https://doi.org/10.1007/s10545-009-1253-2 .
https://doi.org/10.1007/s10545-009-1253-...
], and four presented suboptimal results [1010. Landolt MA, Nuoffer JM, Steinmann B, Superti-Furga A. Quality of life and psychologic adjustment in children and adolescents with early treated phenylketonuria can be normal. J. Pediatr. 2002;140(5):516-521. https://doi.org/10.1067/mpd.2002.123663 .
https://doi.org/10.1067/mpd.2002.123663 ...
-1313. Bik-Multanowski M, Didycz B, Mozrzymas R, et al. Quality of life in noncompliant adults with phenylketonuria after resumption of the diet. J. Inherit. Metab. Dis. 2009;32(1):126. https://doi.org/10.1007/s10545-009-9969-6 PMID:18956249 .
https://doi.org/10.1007/s10545-009-9969-...
]. However, more recent studies suggest that the HRQL of patients with PKU is often comparable to that of the general population [1414. Ziesch B, Weigel J, Thiele A, et al. Tetrahydrobiopterin (BH4) in PKU: effect on dietary treatment, metabolic control, and quality of life. J Inherit Metab Dis. 2012;35(6):983-992. https://doi.org/10.1007/s10545-012-9458-1 .
https://doi.org/10.1007/s10545-012-9458-...
-1818. Bosch AM, Burlina A, Cunningham A, et al. Assessment of the impact of phenylketonuria and its treatment on quality of life of patients and parents from seven European countries. Orphanet J Rare Dis. 2015;10(1):80. https://doi.org/10.1186/s13023-015-0294-x .
https://doi.org/10.1186/s13023-015-0294-...
]. Most of these studies use generic instruments to evaluate HRQL, i.e., questionnaires intended for use irrespective of the underlying disease. The lack of specificity of these generic questionnaires, not specifically designed to address the impact of PKU and its treatment on patients’ lives, might be the reason for observing normal HRQL outcomes. Those generic questionnaires fail to assess more subtle problems that may be experienced by individuals with PKU. For instance, Ziesch et al. [1414. Ziesch B, Weigel J, Thiele A, et al. Tetrahydrobiopterin (BH4) in PKU: effect on dietary treatment, metabolic control, and quality of life. J Inherit Metab Dis. 2012;35(6):983-992. https://doi.org/10.1007/s10545-012-9458-1 .
https://doi.org/10.1007/s10545-012-9458-...
] used the KINDL (Kinder Lebensqualität), a generic measure of HRQL for children (originally developed in German) to assess the impact of BH4 on quality of life. They noticed that HRQL results conflicted with personal reports from children and parents, and suggested that these outcomes could be related to the use of the KINDL which did not capture aspects that mattered to the patients. They concluded that the development of a specific disease-related PKU instrument to assess HRQL could be a useful addition to the field. As such, a HRQL PKU-specific instrument should be able to detect decrease in specific domains important to the life of patients with PKU as well as potential improvements in these domains due to therapeutic interventions.

The phenylketonuria - quality of life (PKU-QOL) questionnaire was developed to address these issues [1919. 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. https://doi.org/10.1186/s13023-015-0261-6 PMID:25958326.
https://doi.org/10.1186/s13023-015-0261-...
]. The PKU-QOL is the first self-administered instrument developed for patients with PKU and their caregivers which assesses three domains important to the patients, i.e., PKU symptoms, PKU in general (i.e., physical, emotional, social and overall impacts of PKU), and the impact of treatment. There are four versions of the PKU-QOL: three are age-specific [Child (9-11 years old) PKU-QOL (40 items), Adolescent (12-17 years old) PKU-QOL (58 items), Adult PKU-QOL (65 items)], and one version, i.e., Parent PKU-QOL (54 items), enables the evaluation of the HRQL of children by their caregivers as well as an assessment of the parents’ HRQL. The four versions share a similar structure, but reflect the specific realities of each population. The PKU-QOL was developed and validated in eight countries (i.e., France, Germany, Italy, The Netherlands, Spain, Turkey, the United Kingdom (UK) and the United States of America (USA) [1919. 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. https://doi.org/10.1186/s13023-015-0261-6 PMID:25958326.
https://doi.org/10.1186/s13023-015-0261-...
, 2020. Jurecki E, Cunningham A, Birardi V, Gagol G, Acquadro C. Development of the US English version of the phenylketonuria - quality of life (PKU-QOL) questionnaire. Health Qual Life Outcomes. 2017 ;15(1):46. https://doi.org/10.1186/s12955-017-0620-1 .
https://doi.org/10.1186/s12955-017-0620-...
]).

The aim of this study was to adapt and linguistically validate the PKU-QOL in Brazilian Portuguese for use in Brazil by healthcare providers to evaluate the HRQL of patients with PKU.

Methods

Linguistic Validation Process

The linguistic validation process [ 2121. Mear I, Giroudet C. Linguistic Validation Procedures. In: Acquadro C, Conway K, Giroudet C, Mear I, eds. Linguistic Validation Manual for Health Outcome Assessments. Lyon, France: Mapi Institute; 2012. 15-117: chap 1. ] used to develop the Brazilian Portuguese version of the PKU-QOL was in compliance with the recommendations of the International Society for Pharmacoeconomics and Outcomes Research [2222. Wild D, Grove A, Martin M, et al. ISPOR Task Force for Translation and Cultural Adaptation. Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes (PRO) Measures: report of the ISPOR Task Force for Translation and Cultural Adaptation. Value Health. 2005;8(2):94-104. . https://doi.org/10.1111/j.1524-4733.2005.04054.x .
https://doi.org/10.1111/j.1524-4733.2005...
, 2323. Wild D, Eremenco S, Mear I, et al. Multinational trials-recommendations on the translations required, approaches to using the same language in different countries, and the approaches to support pooling the data: the ISPOR Patient-Reported Outcomes Translation and Linguistic Validation Good Research Practices Task Force report. Value Health. 2009;12(4):430-440. https://doi.org/10.1111/j.1524-4733.2008.00471.x .
https://doi.org/10.1111/j.1524-4733.2008...
]. The British English questionnaire served as a basis for the validation process of the Brazilian Portuguese PKU-QOL questionnaire. The process, conducted by a coordinating center (i.e., Mapi Language Services), consisted of five steps (Figure 1).

Figure 1
Linguistic Validation Process

The first step involved the conceptual analysis of the original British English PKU-QOL questionnaire, in collaboration with the sponsor of the project, in order to provide the translation team with a document explaining the meaning of each instruction, item and response options and suggesting terms to denote each concept. This was the basis for ensuring that the Brazilian Portuguese version of the PKU-QOL was faithful to the meaning of the original.

Secondly, the original British English PKU-QOL was translated through a dual process of forward-backward translation and reviews by a local team leader and the project manager of the coordinating center who supervised the whole process. Two different Brazilian Portuguese versions were developed independently by two native Brazilian translators living in Brazil; these two versions were used to create one single translation called the reconciled version (i.e., Step 2, forward translation step). The reconciliation process was performed during a meeting involving the two forward translators and the local team leader of the project in Brazil. This reconciled version was back-translated into English (Step 3) and compared to the original British PKU-QOL to check for discrepancies and control the quality of the Brazilian Portuguese reconciled version. The backward translation was performed by a translator blinded to the original US version, native British speaker, fluent in Brazilian Portuguese, and living in Brazil. This document was reviewed by the developer of the original US questionnaire, the local team leader and the project manager of the coordinating center. The objective was to check for discrepancies with the original version due to inaccurate wording in the Brazilian Portuguese reconciled version.

In Step 4 (i.e., testing), the resulting Brazilian Portuguese version (following forward and backward translation steps) was reviewed by three dieticians who provide care to PKU patients, living in different areas of Brazil, to check for the accuracy of the wording and agree on wording that would take into consideration the differences of language between regions. Then, the dieticians-revised version was used for in-depth cognitive individual interviews with patients and caregivers. The objective was to investigate the appropriateness, understandability and clarity of the Brazilian Portuguese PKU-QOL questionnaire. Participants were asked to comment on their understanding of each part of the questionnaire (i.e., instructions, questions and response categories) and suggest alternative formulations where wording was thought to be problematic. The interviewer carefully explored if the patients and their caregivers had a clear understanding of the concept behind each item (Were the participants able to provide the meaning of each item?), and if not why (i.e., inaccurate translation or concept not culturally relevant?). In case of any difficulties, the interviewer also asked for alternative wording. For each instruction, item and response options, all problems identified and suggestions for changes, were gathered in a summary grid and analyzed to produce the final version.

Finally, two proof-readings were conducted by two translators working independently (i.e., the in-country consultant and one translator new to the study (step 5).

Participants

Patients with a diagnosis of PKU were recruited through the Associação de Pais e Amigos dos Excepcionais (APAE) in Sao Paulo, Brazil who agreed to participate in this study. The APAE was asked to recruit patients of specified ages according to the questionnaire being evaluated. Patients and their caregivers were included if they agreed to participate in the interviews, provided informed content, and were native Brazilian Portuguese speakers residing in Brazil. Patients were not recruited based on their phenotype.

Analysis

The linguistic validation report was reviewed to identify difficulties and problematic issues, as well as the solutions proposed to overcome them. The types of difficulties were categorized as Cultural (C), Idiomatic (I), Semantic/conceptual (S) or Syntactic (Sy) (Table 1).

Table 1
Categorization of translation difficulties

Results

Participants

Interviews were conducted with 15 patients and 5 caregivers of patients with PKU (Table 2). The Brazilian Portuguese versions of the PKU-QOL were administered as follows: Child PKU-QOL to five children; Adolescent PKU-QOL to five adolescents; Adult PKU-QOL to five adults; and Parent PKU-QOL to five parents of the children/adolescents already recruited to test the children and adolescent versions.

Table 2
Demographic characteristics of the cognitive interview participants

The questionnaire on the whole was reported to be clearly worded and easy to understand. The instructions, as well as the response choices, were found to be straightforward and free from ambiguity. For each item, respondents had no difficulty in choosing their answer.

The comprehension rates for each category of respondents were the following: children = 90%; adolescents = 91%; adults = 88%; parents = 98%. Those rates correspond to the ration between the number of respondents who had no difficulties in understanding divided by the total number of respondents. Understanding of the title of each domain, each instruction sentence, all items and their corresponding response category was taken into consideration for the rate calculation.

Translation Issues

All issues are presented in details in Table 3.

Table 3
Most problematic PKU-QOL translation issues classified by version (Children, Adolescents, Adults and Parents) and by type of difficulty (Diff.) - Cultural (C), Idiomatic (I), Semantic (S) and Syntactic (Sy)

The main difficulty with all four versions was the use of the acronym “PKU” in the first forward translations. In the original UK, “PKU” refers to the disease, i.e. phenylketonuria. However, during the cognitive interviews, respondents made the confusion between the disease itself and the food supplement since it is written “PKU” or “COMIDA-PKU” on the packaging of the product. Most of the respondents understood PKU as the supplement and not the disease, even though explained in the instructions. Patients know the disease as “fenilcetonúria” or “fenil”, but never as “PKU.” Therefore, it was very confusing to keep “PKU” (referring to the disease), “PKU food,” and “PKU diet” as stated in the original UK version.

Several possibilities were suggested:

1. To keep the acronym PKU when referring to the disease but adding an extra explanation in the instructions, such as:

  • - “On this questionnaire when you read PKU, it means we are asking about fenilcetonuria also called fenil.”

  • - “When you read Formula Metabolica, it means we are asking about the product/powder prescribed by the dietician.”

  • - “When you read PKU diet it means we are asking about the special diet you have to follow.”

2. Another option was training every participant before starting the study, explaining what each term referred to.

3. The third option was not to use the acronym PKU and use fenilcetonuria (fenil) throughout all versions.

Option 3 was chosen in fine following the advice of the dieticians, and discussions with the sponsor. However, to avoid the repetition of the two words throughout the questionnaire and redundancy, it was decided to replace PKU by:

a) fenilcetonúria (fenil), in the title of each version, in the name of the concerned domains (i.e., Diet and Supplement, Daily life, and Feelings in general), and in the instructions, and

b) fenil, in the items (i.e., statements and questions of the PKU-QOL).

A major effort of harmonization was conducted throughout the process, making sure to apply the most appropriate wording to all versions when an interesting solution was found in particular during the cognitive interviews. For instance, the verbal form “may experience” in the instructions of the domain “Your daily life with PKU”, originally translated to “podem viver” was changed to “podem acontecer” (may happen) in all versions following the interviews with the children.

Discussion

The adaptation of the PKU-QOL questionnaire from British English to Brazilian Portuguese did not reveal major semantic or cultural issues. Participating patients with PKU and their caregivers provided input essential to adaptation of the PKU-QOL questionnaire so that each component could be easily understood by the Brazilian target population. The PKU-QOL questionnaire was well accepted by the participants of the study, which supports the assumption that concepts assessed and identified during the development of the original PKU-QOL questionnaire [1919. 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. https://doi.org/10.1186/s13023-015-0261-6 PMID:25958326.
https://doi.org/10.1186/s13023-015-0261-...
] were equally relevant to the Brazilian patients and their caregivers. The main limitations of our research were the following: 1) the use of a convenience sample that represents only a part of the entire population of patients with PKU and their caregivers in Brazil, 2) the research was performed with a PKU population from the most developed Brazilian state in educational and economic aspects [2424. United Nations Development Programme, Institute of Applied Economic Research, João Pinheiro Foundation. Atlas of Human development in Brazil. http://atlasbrasil.org.br/2013/en/ranking. Last accessed 09/11/2018.
http://atlasbrasil.org.br/2013/en/rankin...
]; and 3) we did not recruit patients based on their phenotype. Our intent was to test how well the patients understood the questionnaire, and whether or not the wording was clear and explicit, and not to test the content validity of the Brazilian PKU-QOL. Nevertheless, we acknowledge that, for the future use of the PKU-QOL, disease phenotype is relevant as the degree of dietary PHE restriction is impacted by this. When the PKU-QOL questionnaires are updated in the future, it is intended to include a sentence acknowledging that some patients may not require some treatment components (medical food, special low protein food, etc.), and that the questions should be answered accordingly.

Besides the initial papers published on the development and use of the PKU-QOL questionnaire in eight countries [1818. Bosch AM, Burlina A, Cunningham A, et al. Assessment of the impact of phenylketonuria and its treatment on quality of life of patients and parents from seven European countries. Orphanet J Rare Dis. 2015;10(1):80. https://doi.org/10.1186/s13023-015-0294-x .
https://doi.org/10.1186/s13023-015-0294-...
-2020. Jurecki E, Cunningham A, Birardi V, Gagol G, Acquadro C. Development of the US English version of the phenylketonuria - quality of life (PKU-QOL) questionnaire. Health Qual Life Outcomes. 2017 ;15(1):46. https://doi.org/10.1186/s12955-017-0620-1 .
https://doi.org/10.1186/s12955-017-0620-...
], published research on cross-cultural perspectives of quality of life of patients with PKU is limited [2525. Keil S, Anjema K, van Spronsen FJ, et al. Long-term follow-up and outcome of phenylketonuria patients on sapropterin: a retrospective study. Pediatrics. 2013;131(6):e1881-e1888. https://doi.org/10.1542/peds.2012-3291 .
https://doi.org/10.1542/peds.2012-3291 ...
]. Most of the cross-cultural evaluations currently published review diagnostic and management perspectives in various countries or contexts such as immigration [2626. Giżewska M, MacDonald A, Bélanger-Quintana A, et al. Diagnostic and management practices for phenylketonuria in 19 countries of the South and Eastern European Region: survey results. Eur J Pediatr. 2016;175(2):261-272. https://doi.org/10.1007/s00431-015-2622-5 .
https://doi.org/10.1007/s00431-015-2622-...
-3131 Ipsiroglu OS, Herle M, Spoula E, et al. Transcultural pediatrics: compliance and outcome of phenylketonuria patients from families with an immigration background. Wien Klin Wochenschr. 2005;117(15-16):541-547. https://doi.org/10.1007/s00508-005-0327-x .
https://doi.org/10.1007/s00508-005-0327-...
]. The availability of the PKU-QOL questionnaire in nine countries (i.e., Brazil, France, Germany, Italy, The Netherlands, Spain, Turkey, UK and the US) will enable cross-cultural research in PKU, and might be the first step to use in various cultural settings. International studies assessing differences of impact across cultures would allow cross-cultural comparisons and improve awareness, tracking, and management of impact on HRQL in patients with PKU in different cultures, thus providing opportunity for increased support. In addition, the cross-cultural equivalence of the nine language versions of the PKU-QOL questionnaire (due to the use of rigorous cross-cultural methodologies [1919. 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. https://doi.org/10.1186/s13023-015-0261-6 PMID:25958326.
https://doi.org/10.1186/s13023-015-0261-...
-2020. Jurecki E, Cunningham A, Birardi V, Gagol G, Acquadro C. Development of the US English version of the phenylketonuria - quality of life (PKU-QOL) questionnaire. Health Qual Life Outcomes. 2017 ;15(1):46. https://doi.org/10.1186/s12955-017-0620-1 .
https://doi.org/10.1186/s12955-017-0620-...
] during the development phase), will enable the pooling of data gathered in different countries, and optimize the chance of demonstrating treatment benefit. This will be useful in assessing the impact of standard dietary treatment, pharmacological treatments such as sapropterin, and potential new therapies on clinical outcomes.

Thanks to the availability of the PKU-QOL questionnaire into Brazilian Portuguese, the patients’ perceptions in Brazil will be assessed and documented as patients age. This will enable increased understanding of the impact of PKU on the HRQL of patients and their parents throughout their life cycle. The PKU-QOL questionnaire is a validated tool and its use in assessing the impact of standard dietary therapy, pharmacological treatments such as sapropterin, and potential new therapies on the patients’ life and their caregivers’ will be valuable in the management of patients with PKU in the future. In addition, the use of this instrument will encourage collection of data consistent across treatment centers in Brazil.

Conclusions

The adaptation of the British English PKU-QOL questionnaire into Brazilian Portuguese did not raise major semantic and cultural issues. The four versions of the PKU-QOL questionnaire are now fully linguistically validated in Brazilian Portuguese. The PKU-QOL questionnaire will be valuable for Brazilian healthcare providers in individualizing treatment and managing patients with PKU.

Abbreviations

BH4: tetrahydrobiopterin; C: Cultural; FDA: Food and Drug Administration; HRQL: Health-related quality of life; I: Idiomatic; KINDL: Kinder Lebensqualität; PAH: Phenylalanine hydroxylase; PAHD: Phenylalanine hydroxylase deficiency; PHE: Phenylalanine; PKU: Phenylketonuria; PKU-QOL: Phenylketonuria - quality of life; QOL: Quality of life; S: Semantic; Sy: Syntactic; TYR: Tyrosine. UK: United Kingdom; USA: United States of America.

Acknowledgements

We are extremely grateful to the patients, caregivers and the clinician who have contributed to this study.

References

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    » https://doi.org/10.1016/S0140-6736(10)60961-0
  • 2. Waisbren SE, Noel K, Fahrbach K, et al. Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis. Mol Genet Metab 2007;92(1-2):63-70. https://doi.org/10.1016/j.ymgme.2007.05.006 PMID:17591452 .
    » https://doi.org/10.1016/j.ymgme.2007.05.006
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    » https://doi.org/10.1038/gim.2013.157
  • 4. Camp KM, Lloyd-Puryear MA, Huntington KL. Nutritional treatment for inborn errors of metabolism: indications, regulations, and availability of medical foods and dietary supplements using phenylketonuria as an example. Mol Genet Metab 2012;107(1-2):3-9. https://doi.org/10.1016/j.ymgme.2012.07.005
    » https://doi.org/10.1016/j.ymgme.2012.07.005
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    » https://doi.org/10.1038/gim.2013.179
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  • Competing interests

    EJ is employee and stock owner of BioMarin Pharmaceutical Inc., USA. FV, DG are employees of BioMarin Brasil Farmacêutica Ltda, Brazil. CA is an employee of Mapi, France, an ICON plc Company, a consulting company commissioned by BioMarin Pharmaceutical Inc., USA. ARF and EL are dieticians, employees of APAE (São Paulo and Salvador, Brazil); LG is dietician, employee of the Hospital das Clínicas de Porto Alegre, Brazil.
  • Funding

    The study was funded by BioMarin Pharmaceutical Inc.
  • Ethics approval and consent to participate

    All study subjects gave informed, written consent prior to their participation; consent on behalf of all children taking part was given in writing by their parents or guardians. No submission to Ethical Committee was required.
  • Intellectual property and condition of use

    The PKU-QOL questionnaire is available in four versions: Child PKU-QOL, Adolescent PKU-QOL, Adult PKU-QOL and Parent PKU-QOL. The PKU-QOL is protected by international copyright – PKU-QOL © BioMarin Pharmaceutical Inc. – 2015 – All Rights Reserved. The PKU-QOL is available freely for use in individual medical practice and in non-privately funded academic research. Access to the questionnaire, as well as further information on, or permission to use the PKU-QOL and/or translations, can be found on https://eprovide.mapi-trust.org/ instruments/phenylketonuria-impact-and-treatment-qualityof- life-questionnaire. Potential users will have to create an account on eProvide (link to https://eprovide.mapi-trust.org/register ) and specify in the Organization field that they are a clinician. This categorization will enable free access to the PKU-QOL and its translations. A software called “PKU-QoL© Electronic scorer” is available to ease the calculation of PKU-QOL scores for all four versions. This software and QuickStart guide can be downloaded from the following link: https://iconplc.box.com/v/PKU-QOLelectronic- scorer.

Publication Dates

  • Publication in this collection
    07 Mar 2019
  • Date of issue
    2019

History

  • Received
    02 Oct 2018
  • Accepted
    14 Nov 2018
Latin American Society Inborn Errors and Neonatal Screening (SLEIMPN); Instituto Genética para Todos (IGPT) Rua Ramiro Barcelos, 2350, CEP: 90035-903, Porto Alegre, RS - Brasil, Tel.: 55-51-3359-6338, Fax: 55-51-3359-8010 - Porto Alegre - RS - Brazil
E-mail: rgiugliani@hcpa.edu.br