Open Access Research

Measuring patient experiences in Fabry disease: validation of the Fabry-specific Pediatric Health and Pain Questionnaire (FPHPQ)

Uma Ramaswami1*, Donald E Stull2, Rossella Parini3, Guillem Pintos-Morell4, Catharina Whybra5, Gisela Kalkum5, Marianne Rohrbach6, Mireia Raluy-Callado7, Michael Beck5, Wen-Hung Chen8, Ingela Wiklund7 and on behalf of the FOS Investigators

Author Affiliations

1 The Willink Biochemical Genetics Unit, Genetic Medicine, St Mary’s Hospital, Manchester, UK

2 RTI Health Solutions, Manchester, UK

3 San Gerardo Hospital, Università Milano Bicocca, Monza, Italy

4 Department of Pediatrics, “Germans Trias i Pujol” Hospital, Universitat Autònoma de Barcelona, Badalona, Spain

5 Department of Pediatrics, University Medical Center, University of Mainz, Mainz, Germany

6 University Children's Hospital, Zurich, Switzerland

7 United BioSource Corporation, London, UK

8 United BioSource Corporation, Bethesda, MD, USA

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Health and Quality of Life Outcomes 2012, 10:116  doi:10.1186/1477-7525-10-116

Published: 20 September 2012



Common symptoms for children with Anderson-Fabry Disease (FD) such as acroparaesthesia and gastrointestinal manifestations can only be objectively assessed in patients using a valid instrument. To date, no such instrument exists.


A preliminary 40-item measure of symptoms and experience with FD, the Fabry-specific Paediatric Health and Pain Questionnaire (FPHPQ) was developed, but lacked a formal assessment of its measurement properties. The FPHPQ was used in the Fabry Outcome Survey (FOS), a registry for all patients with a confirmed diagnosis of FD who are receiving agalsidase alfa, or are treatment naïve and who are managed by physicians participating in FOS. After an item analysis to explore how items performed and combined into domains, a battery of psychometric analyses was performed to assess the measurement properties of this new instrument.


Eighty-seven children (ages 4-18 years) completed the questionnaire. Twenty-three items in three subscales of the questionnaire emerged: pain associated with heat or exertion, pain associated with cold, and abdominal pain and fatigue symptoms. Internal consistency reliability for all three subscales was good (Cronbach alpha ≥ 0.84). Reliability was equally high for all age groups (4-7, 8-12, and 13-18). Test-retest reliability was high for all three subscales (intraclass correlation coefficient ≥ 0.74). Construct validity was demonstrated by moderate correlation with brief pain inventory (BPI), KINDL, and EQ-5D. Known group validity showed all subscales were able to discriminate between Fabry disease severity groups as classified by above or below median of the FOS MSSI (Mainz Severity Score Index) grade. The heat or exertion subscale was responsive to change in symptoms between responders and non-responders as defined by change in EQ-5D index scores between the first and second visit.


Preliminary results indicate that the measurement properties of FPHPQ are valid and reliable for assessing patient-reported symptoms of FD. The questionnaire could be a useful tool for clinicians to understand the progression of disease and monitor treatment effects. FPHPQ will be further validated and refined as the FOS registry is continuously adding more patients.

Fabry disease; Enzyme replacement therapy; Children; Paediatric Health and Pain Questionnaire; Psychometrics validation