This is an analysis of the prospective, multicenter, observational cohort study and patient registry “Growth and comorbidity in children with X-linked hypophosphatemic rickets” of the German Society for Pediatric Nephrology (GPN) and the German Society for Pediatric and Adolescent Endocrinology and Diabetology (DGPAED), initiated in 2018 [14]. The study/registry received appropriate ethics committee approval from the Institutional Ethics Review Board at Hannover Medical School (No. 7259) and from each participating center and was performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from all parents/guardians, with age-appropriate consent or assent from patients.

In this study/registry, children and adolescents were eligible if diagnosed with XLH based on family history and/or genetic confirmation, presence of clinical and/or radiological signs of rickets, impaired growth velocity and serum phosphate levels below the age-related reference range, associated with selective renal phosphate wasting, i.e., reduced age-related maximal rate of tubular phosphate reabsorption divided by the glomerular filtration rate (TmP/GFR) using a 2nd morning spot urine and parallel blood sampling, in the absence of vitamin D or calcium deficiency [2, 4]. A total of 134 pediatric XLH patients aged between 0.1 and 18 years were enrolled in Germany between November 2018 and May 2023. One hundred of these patients were aged between 8 and 18 years which was the inclusion criteria for the study on HRQoL. The KIDSCREEN questionnaires were developed on a sample of children and adolescents at this age. The items were developed for this target group; normal values are offered and the T-values were calculated. It has been shown that younger children do not understand some questions or that some questions are inappropriate in this age group. In total, 63 children and adolescents agreed to participate in the HRQoL survey and 23 of those in qualitative interviews, respectively. Due to the interdisciplinary approach, a paper-based survey (KIDSCREEN-52) was used and supplemented with guided telephone interviews with children and adolescents or their caregivers. This allowed a deeper insight into this complex matter. With this approach, we respect the bio-psycho-social model of the International Classification of Functioning, Disability and Health (ICF). The ICF of the World Health Organization (WHO) is intended to enable internationally uniform communication on the effects of health problems, taking into account the entire life background of a person [15]. The ICD-based XLH diagnosis was expanded with additional information on contextual factors so that a broader and more appropriate picture of the HRQoL of the children and adolescents with XLH is possible. The bio-psycho-social model considers functional impairment in interaction with contextual factors. The contextual factors include both environmental and personal factors. The contextual factors are often influenced by the social environment. Quality of life is thus not primarily recognized as a person’s medical problem, but as a socially determined problem [16].

The standardized questionnaires KIDSCREEN-52 (child and adolescent version 8 to 18 years for Germany) and the KIDSCREEN-52 (parents’ version for Germany) comprises 52 questions in ten dimensions: Physical Well-Being (5 items), Psychological Well-Being (6 items), Moods and Emotions (7 items), Self-Perception (5 items), Autonomy (5 items), Parent Relations and Home Life (6 items), Financial Resources (3 items), Peers and Social Support (6 items), School Environment (6 items), and Bullying (3 items). KIDSCREEN-52 has five possible answers for each dimension, scored from 1 to 5 [17].

All questionnaires were anonymous. Due to the usual low number of cases of rare diseases, datasets with only one missing item were also included in the analysis. Eight KIDSCREEN-52 questionnaires (3 Self-report/5 Proxy) had more than one missing item, so they could not be used for the evaluation. The KIDSCREEN-52 survey tool continues to be a usable and valid survey tool because socio-demographic correlations as well as judgment effects are consistent. Age- and gender-specific norm scores could be determined using a large and nationally representative sample [18]. Thus, very comprehensive information on psychometric properties in classical and probabilistic test theory is available for both the KIDSCREEN-27 (27 questions) and KIDSCREEN-10 (10 questions) indices in self and parental judgment. Both procedures are widespread and proven, and allow for a fair comparison of HRQoL in children and adolescents from different European countries because of their internationally conducted validation and standardization [18,19,20]. KIDSCREEN is validated and used in studies worldwide. Most articles are published in Spain, followed by Portugal. Overall, more articles are published in Europe than in the rest of the world. In South America, Asia, Africa, North America, Oceania, and Central America, a total of 60 publications have been published [21].

All XLH patients included in this registry were asked by their treating physician to complete the questionnaires and participate later on in the standardized telephone interviews when they visited the outpatient clinic. They had the opportunity to decide for themselves whether or not they wanted to complete the questionnaire and participate in the telephone interviews.

Based on the dimensions of the KIDSCREEN-52 questionnaire, an open interview guideline with in-depth questions was developed, which is based on a multidimensional construct of HRQoL. The structured interview was designed to prevent inconsistency in responses. The questions are standardized and were asked by the same specially trained research assistant to reduce variability in responses. There is a standardized guide to reduce subjectivity in the interpretation of questions. To ensure construct validity, the questions were structured using the ten predetermined items from the internationally recognized and validated KIDSCREEN questionnaire. To ensure content validity, we also conducted expert interviews. After extensive literature research, expert interviews, and a pretest, two items were removed. Questions on Parent Relations and Home Life and Financial Resources were felt to be too personal for a telephone interview. The interviewees’ feedback on the comprehensibility of the structured interview was positive. After obtaining informed consent, implementation took place in the form of telephone interviews of approximately 1 h in duration, which were recorded as audio files and then transcribed. In the course of the proxy interviews, representatives were always reminded to take the perspective of the interviewee as much as possible, taking into account individual experiences. As the state of research on the HRQoL of patients with XLH is rudimentary and, accordingly, few robust hypotheses can be used, the principle of openness represents an essential approach in this procedure. In this respect, the subjective perspective of those affected takes on a central role. During the interview situation, a comprehensive overview of the reality of life with XLH is made possible through individual assessments. Furthermore, the interview situation offers the possibility of clarifying misunderstandings and allows a more precise understanding of complex and individual topics such as HRQoL. For example, the subjective significance of the XLH condition for the assessment of quality of life can be determined and other relevant factors can be collected. Furthermore, additional research-guiding hypotheses can be generated. This mixed-methods design enables a comprehensive, both comparable and individual, assessment of the HRQoL of the patient group.

The KIDSCREEN Group Europe recommends two methods to analyze the obtained data. One is to evaluate and analyze the data through SPSS statistical and analysis software [17]. This method was used for this survey. The first step was to create the “Data mask” and to enter the data from each of the last surveys. This step was done in close accordance with the English Data mask as well as the manual [17]. In the next step, data were summarized along the ten dimensions and T-values were generated using the KIDSCREEN-52 syntax. This allowed for international referencing of the results. The values are based on data from 12 European countries. Following the recommendations of the KIDSCREEN Group European data will be compared between group scores on the KIDSCREEN scales and the reference population [17]. For this purpose, the mean values and standard deviations of the dimensions are used (Table 1) as well as the T-values, which are compared with international and German T-values. A qualitative content analysis was carried out using MAXQDA software. The individual interview files were given predefined codes based on the question items of the interview guide. With the help of the codes, the content allocation of the statements and the analysis of the interviews were implemented. Data is presented as mean ± SD or median (IQR) according to Shapiro-Wilk normality tests. All statistical analyses were performed with IBM SPSS Statistics version 29.