Quality of life of children affected by rare diseases: a systematic review and meta-analysis

El objetivo de este estudio fue analizar, mediante una revisión sistemática y meta-análisis, la calidad de vida (CV) percibida en niños diagnosticados con enfermedades raras, así como examinar los posibles factores moderadores asociados. Se identificaron 24 muestras (k = 24; N = 1030) en 8 estudios que cumplían los criterios de inclusión. Los resultados del meta-análisis mostraron buenos niveles de calidad de vida, aunque inferiores en comparación con la población general y se observó una heterogeneidad sustancial entre estudios (I² = 86.7%). Los análisis de meta-regresión revelaron efectos moderadores significativos para la región geográfica, el tipo de instrumento de evaluación y el tipo de enfermedad. No se hallaron indicios de sesgo de publicación (prueba de Egger, p = .62). Estos resultados subrayan la necesidad de mejorar la atención integral, la coordinación sanitaria y el apoyo psicosocial para estos pacientes y sus familias.

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Adedeji, A., Witt, S., Innig, F., Alves, I., Provasi, C., Sessa, M., Mohnike, K., & Quitmann, J. (2025). Coping and quality of life of parents of children with achondroplasia: A narrative review. Frontiers in Medicine, 12, 1500389. https://doi.org/10.3389/fmed.2025.1500389

Aiyegbusi, O. L., Isa, F., Kyte, D., Pankhurst, T., Kerecuk, L., Ferguson, J., Lipkin, G., & Calvert, M. (2020). Patient and clinician opinions of patient reported outcome measures (PROMs) in the management of patients with rare diseases: a qualitative study. Health and quality of life outcomes, 18(1), 1-12.

https://doi.org/10.1186/s12955-020-01438-5

Assalone, F., Ortega, J., Vázquez, N., & Vázquez, V. (2024). Systematic review on family functioning in families of children with rare diseases. Papeles del Psicólogo / Psychologist Papers, 45(1), 39–47. https://doi.org/10.23923/pap.psicol.3031

Atkins, J. C., & Padgett, C. R. (2024). Living with a rare disease: Psychosocial impacts for parents and family members – A systematic review. Journal of Child and Family Studies, 33, 617–636. https://doi.org/10.1007/s10826-024-02790-6

Benjamin, K., Vernon, M. K., Patrick, D. L., Perfetto, E., Nestler-Parr, S., & Burke, L. (2017). Patient-reported outcome and observer-reported outcome assessment in rare disease clinical trials: an ISPOR COA emerging good practices task force report. Value in Health, 20(7), 838-855. https://doi.org/10.1016/j.jval.2017.05.015

Berman, J. J. (2014). Rare diseases and orphan drugs: keys to understanding and treating the common diseases. Academic Press.

Boettcher, J., Boettcher, M., Wiegand-Grefe, S. & Zapf, H. (2021). Being the Pillar for Children with Rare Diseases—A Systematic Review on Parental Quality of Life. International Journal of Environmental Research and Public Health, 18, 4993. https://doi.org/10.3390/ijerph18094993

Boettcher, J., Zapf, H., Fuerboeter, M., Nazarian, R., Reinshagen, K., Wiegand-Grefe, S., & Boettcher, M. (2021). Perceived mental health in parents of children with rare congenital surgical diseases: a double ABCX model considering gender. Orphanet Journal of Rare Diseases, 16(1), 1-10. https://doi.org/10.1186/s13023-021-01998-9

Bonett, D. G., & Price Jr, R. M. (2015). Varying coefficient meta-analysis methods for odds ratios and risk ratios. Psychological methods, 20(3), 394. https://doi.org/10.1037/met0000032

Borenstein, M., Hedges, L. V., Higgins, J. P. T. & Rothstein, H. R. (2021). Introduction to meta-analysis (2nd ed.). Wiley.

Bosch, A. M., Burlina, A., Cunningham, A., Bettiol, E., Moreau-Stucker, F., Koledova, E., Benmedjahed, K. & Regnault, A. (2015). Assessment of the impact of phenylketonuria and its treatment on quality of life of patients and parents from seven European countries. Orphanet journal of rare diseases, 10(1), 1-14. https://doi.org/10.1186/s13023-015-0294-x

Botella, J. & Sánchez, J. (2015). Meta-análisis en ciencias sociales y de la salud. Síntesis.

Botella, J., & Gambara, H. (2002). Qué es el meta-análisis. Biblioteca nueva.

Cardinali, P., Migliorini, L., & Rania, N. (2019). The caregiving experiences of fathers and mothers of children with rare diseases in Italy: Challenges and social support perceptions. Frontiers in psychology, 10, 1780. https://doi.org/10.3389/fpsyg.2019.01780

Caliandro, P., Grugni, G., Padua, L., Kodra, Y., Tonali, P., Gargantini, L., Ragusa, L., Crinò, A. & Taruscio, D. (2007). Quality of life assessment in a sample of patients affected by Prader–Willi syndrome. Journal of paediatrics and child health, 43(12), 826-830. https://doi.org/10.1111/j.1440-1754.2007.01200.x

Coca, J. R., Gómez-Redondo, S., Soto-Sánchez, A., Lozano-Blasco, R., & RomeroGonzalez, B. (2023). Perception of Social and Educational Quality of Life of Minors Diagnosed with Rare Diseases: A Systematic Review and Meta-Analysis. International Journal of Environmental Research and Public Health, 20(2), 933. https://doi.org/10.3390/ijerph20020933

Chu, S. Y., Wen, C. C., & Weng, C. Y. (2022). Gender Differences in Caring for Children with Genetic or Rare Diseases: A Mixed-Methods Study. Children, 9(5), 627. https://doi.org/10.3390/children9050627

Cole, T., McKendrick, F., Titman, P., Cant, A. J., Pearce, M. S., Cale, C. M., Goldblatt, D., & Gennery, A. R. (2013). Health related quality of life and emotional health in children with chronic granulomatous disease: a comparison of those managed conservatively with those that have undergone haematopoietic stem cell transplant. Journal of clinical immunology, 33(1), 8-13. https://doi.org/10.1007/s10875-012-9758-0

Courbier, S., & Berjonneau, E. (2017). Juggling care and daily life: the balancing act of the rare disease community. A Rare Barometer survey. Eurordis. Retrieved from: http://download2.eurordis.org.s3.amazonaws.com/rbv/2017_05_09_Social%20survey%20leaflet%20final.pdf

Czech, M., Baran-Kooiker, A., Atikeler, K., Demirtshyan, M., Gaitova, K., HolowniaVoloskova, M., ... & Sykut-Cegielska, J. (2020). A review of rare disease policies and orphan drug reimbursement systems in 12 Eurasian countries. Frontiers in public health, 7:416. https://doi.org/10.3389/fpubh.2019.00416

Dawkins, H. S. J., Draghia-Akli, R., Lask, P., Lau5, L. P. L., Jonker5, A. H., Cutillo, C. M., Rath, A., Boycott, K. M., Baynam, G Lochmüller, H., Kaufmann, P., Le Cam, Y., Hivert, V., & Austin, C. P. (2018). Progress in Rare Diseases Research 2010–2016: An IRDiRC Perspective. Clinical and Translational Science, 11, 11–20. https://doi.org/10.1111/cts.12501

De Clercq, E., Schmieg, H. V., Gregorowius, D. et al. Quality of life among children and young adults with rare diseases. A parental perspective. Eur J Pediatr 184, 510 (2025). https://doi.org/10.1007/s00431-025-06293-4

Der Simonian, R. & Laird, N. (2015). Meta-analysis in clinical trials revisited. Contemporary Clinical Trials, 45: 139–145. https://doi.org/10.1016/j.cct.2015.09.002

Downes, M. J., Brennan, M. L., Williams, H. C., & Dean, R. S. (2016). Development of a critical appraisal tool to assess the quality of cross-sectional studies (AXIS). BMJ open, 6(12), e011458. http://dx.doi.org/10.1136/bmjopen-2016-011458

Dumbuya, J. S., Zeng, C., Deng, L., Li, Y., Chen, X., Ahmad, B., & Lu, J. (2025). The impact of rare diseases on the quality of life in paediatric patients: current status. Frontiers in Public Health, 13, 1531583. https://doi.org/10.3389/fpubh.2025.1531583

Eggers, J. (1997). Nonlinear dynamics and breakup of free-surface flows. Reviews of modern physics, 69(3): 865. https://doi.org/10.1103/RevModPhys.69.865

European Commission, Directorate-General for Research and Innovation (2017). Rare diseases: a major unmet medical need. Brussels: RTD-Publications. https://data.europa.eu/doi/10.2777/749056

Eurordis. European Organization for Rare Disorders. (2005). Rare Diseases: understanding this Public Health Priority. Available at: http://www.eurordis.org/IMG/pdf/Princeps_document-SN.pdf

[access: 06/30/2022]

Federación Española de Enfermedades Raras (FEDER). Available at: https://www.enfermedades-raras.org/feder-presenta-su-proyecto-la-perspectiva-de-genero-en-las-er-en-el-marco-de-la-i-jornada-igualdad-de-genero-y-enfermedades-raras

[access: 26/07/2022]

Friese, M. & Frankenbach, J. (2020). p-Hacking and publication bias interact to distort meta-analytic effect size estimates. Psychological Methods, 25(4), 456-471. https://doi.org/10.1037/met0000246

Fuerboeter, M., Boettcher, J, Barkmann, C., Zapf, H., Nazarian, R., Wiegand-Grefe, S., Reinshagen, K. & Boettcher, M. (2021). Quality of life and mental health of children with rare congenital surgical diseases and their parents during the COVID-19 pandemic. Orphanet Journal of Rare Diseases, 16(1), 498. https://doi.org/10.1186/s13023-021-02129-0

Groft, S. C. & Posada, M. (2017). “Rare Diseases: Joining Mainstream Research and Treatment Bases on Reliable Epidemiological Data”, in Posada, M., Taruscio, D. y Groft, S. C. (Ed.) Rare Diseases Epidemiology: Update and Overview. Advances in Experimental Medicine and Biology, 1031. Springer.

Haendel, M., Vasilevsky, N., Unni, D., Bologa, C., Harris, N., Rehm, H., ... & Oprea, T. I. (2020). How many rare diseases are there?. Nature Reviews Drug Discovery, 19(2), 77-78. https://doi.org/10.1038/d41573-019-00180-y

Hendriksz, C. J., Lavery, C., Coker, M., Ucar, S. K., Jain, M., Bell, L., & Lampe, C. (2014). Burden of disease in patients with Morquio A syndrome: results from an international patient-reported outcomes survey. Orphanet journal of rare diseases, 9(1), 1-8. https://doi.org/10.1186/1750-1172-9-32

Higgins, J. P. T. & Green, S. (2011). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration. www.cochrane-handbook.org

Hunter, J. E. & Schmidt, F. L. (2004). Methods of meta-analysis: Correcting error and bias in research findings. Sage. http://dx.doi.org/10.4135/9781483398105

Inoguchi, T. & Shin, D. C. (2009). The Quality of Life in Confucian Asia: From Physical Welfare to Subjective Well-being. Social Indicators Research, 92, 183–190. https://doi.org/10.1007/s11205-008-9352-2

Jak, S. & Cheung, M. W. L. (2019). Meta-analytic structural equation modeling with moderating effects on SEM Parameters. Psychological Methods, 25(4): 430–455. https://doi.org/10.1037/met0000245

Kagawa-Singer, M., Padilla, G. V., & Ashing-Giwa, K. (2010). Health-related quality of life and culture. Seminars in oncology nursing, 26(1), 59-67. https://doi.org/10.1016/j.soncn.2009.11.008

Koto, Y., Ueki, S., Yamakawa, M., & Sakai, N. (2023). Experiences of patients and their family members with metachromatic leukodystrophy, adrenoleukodystrophy, and Krabbe disease: A qualitative systematic review protocol. JBI Evidence Synthesis, 21(5), 1027–1033. https://doi.org/10.11124/JBIES-22-00154

Li, L., Wang, H. M., & Shen, Y. (2003). Chinese SF-36 Health Survey: translation, cultural adaptation, validation, and normalisation. Journal of Epidemiology & Community Health, 57(4), 259-263. http://dx.doi.org/10.1136/jech.57.4.259

Martin-Andrés, A. & Luna del Castillo, J. (2004). Bioestadística para las Ciencias de la Salud. Ediciones Norma - Capitel.

Mascalzoni, D., Petrini, C., Taruscio, D. & Dainotti, S. (2017). The Role of Solidarity (-ies) in Rare Diseases Research, in Posada de la Paz, M., Taruscio, D. y Groft, S. C. (Ed.) Rare Diseases Epidemiology: Update and Overview. Advances in Experimental Medicine and Biology, 1031. Springer.

Might, M. & Crouse, A. B. (2022). Why rare disease needs precision medicine – and why precision medicine needs rare disease. Cell Reports Medicine, 3, 100530. https://doi.org/10.1016/j.xcrm.2022.100530

Moorhouse, J. A., Ellis, H., Horscroft, J. A., Chapman, A., & Akehurst, R. (2018). Policies and Processes Applicable to Drugs for Very Rare Diseases in Australia, Canada, England, France and Germany. Value in Health, 21, S93. https://doi.org/10.1016/j.jval.2018.04.626

Moreau, D. & Gamble, B. (2020). Conducting a meta-analysis in the age of open science: Tools, tips, and practical recommendations. Psychological Methods, 7, 1-19. https://doi.org/10.31234/osf.io/t5dwg

Navarrete-Opazo, A. A., Singh, M., Tisdale, A., Cutillo, C. M., & Garrison, S. R. (2021). Can you hear us now? The impact of health-care utilization by rare disease patients in the United States. Genetics in Medicine, 23(11), 2194-2201. https://doi.org/10.1038/s41436-021-01241-7

Nevin, S. M., McGill, B. C., Kelada, L., et al. (2023). The psychosocial impact of childhood dementia on children and their parents: A systematic review. Orphanet Journal of Rare Diseases, 18, 277. https://doi.org/10.1186/s13023-023-02859-3

Obregón, L. J., Coca, J. R., Plaza Gómez, N., & Gómez Redondo, G. (2025). Rare diseases and socio-educational dimension: a systematic review. International Journal of Inclusive Education, 1-22. https://doi.org/10.1080/13603116.2025.2577267

Orphanet. The portal for rare diseases and orphan drugs. https://www.orpha.net/consor/cgibin/index.php?lng=EN

[access: 07/01/2022]

Paz-Lourido, B., Negre, F., de la Iglesia, B., & Verger, S. (2020). Influence of schooling on the health-related quality of life of children with rare diseases. Health and quality of life outcomes, 18(1), 1-9. https://doi.org/10.1186/s12955-020-01351-x

Pelentsov, L. J., Fielder, A. L., Laws, T. A., & Esterman, A. J. (2016). The supportive care needs of parents with a child with a rare disease: results of an online survey. BMC family practice, 17(1), 1-13. https://doi.org/10.1186/s12875-016-0488-x

PRISMA-Statement website. PRISMA translations policy. http://www.prisma-statement.org/PRISMAStatement/

Qi, X., Xu, J., Shan, L., Li, Y., Cui, Y., Liu, H., Wang, K., Gao, L., Kang, Z., & Wu, Q. (2021). Economic burden and health related quality of life of ultra-rare Gaucher disease in China. Orphanet journal of rare diseases, 16(1), 1-12. https://doi.org/10.1186/s13023-021-01963-6

Ratcliffe, J., Huynh, E., Chen, G., Stevens, K., Swait, J., Brazier, J., ... & Flynn, T. (2016). Valuing the child health utility 9D: using profile case best worst scaling methods to develop a new adolescent specific scoring algorithm. Social Science & Medicine, 157, 48-59. https://doi.org/10.1016/j.socscimed.2016.03.042

Ringold, S., Wallace, C. A., & Rivara, F. P. (2009). Health-related quality of life, physical function, fatigue, and disease activity in children with established polyarticular juvenile idiopathic arthritis. The Journal of rheumatology, 36(6), 1330-1336. https://doi.org/10.3899/jrheum.081028

Roessler, H. I., Knoers, N. V., van Haelst, M. M., & van Haaften, G. (2021). Drug repurposing for rare diseases. Trends in Pharmacological Sciences, 42(4), 255-267. https://doi.org/10.1016/j.tips.2021.01.003

Ruperto, N., Ravelli, A., Pistorio, A., Malattia, C., Viola, S., Cavuto, S., ... & Paediatric Rheumatology International Trials Organisation. (2001). The Italian version of the childhood health assessment questionnaire (CHAQ) and the child health questionnaire (CHQ). Clinical and experimental rheumatology, 19(4; SUPP/23), S91-S95.

Salvatore, M., Polizzi, A., De Stefano, M. C., Floridia, G., Baldovino, S., Roccatello, D., Sciascia, S., Menegatti, E., Remuzzi, G., Dania E., Iatropoulos, P., Bembi, B., Da Riol, R. M., Ferlini, A., Neri, M., Novelli, G., Sanqiuolo, F., Brancati, F., & Taruscio, D. (2020). Improving diagnosis for rare diseases: the experience of the Italian undiagnosed Rare diseases network. Italian Journal of Pediatrics, 46(1), 1-15. https://doi.org/10.1186/s13052-020-00883-8

Slade, A., Isa, F., Kyte, D., Pankhurst, T., Kerecuk, L., Ferguson, J., Lipkin, G., & Calvert, M. (2018). Patient reported outcome measures in rare diseases: a narrative review. Orphanet Journal of Rare Diseases, 13(1), 1-9. https://doi.org/10.1186/s13023-018-0810-x

Smith, C. E., Bergman, P., & Hagey, D. W. (2022). Estimating the number of diseases–the concept of rare, ultra-rare and hyper-rare. iScience, 104698. https://doi.org/10.1016/j.isci.2022.104698

Somanadhan, S., O'Donnell, R., Bracken, S., McNulty, S., Sweeney, A., O'Toole, D., ... & Kroll, T. (2023). Children and young people's experiences of living with rare diseases: An integrative review. Journal of pediatric nursing, 68, e16-e26. https://doi.org/10.1016/j.pedn.2022.10.014

Sterne, J. A., Sutton, A. J., Ioannidis, J. P., Terrin, N., Jones, D. R., Lau, J., Carpenter, J., Rücker, G., Harbord, R. M., Schmid, C. H., Tetzlaff, J., Deeks, J. J., Peters, J., Macaskill, P., Schwarzer, G., Duval, S., Altman, D. G., Moher, D., & Higgins, J. P. (2011). Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ (Clinical research ed.), 343, d4002. https://doi.org/10.1136/bmj.d4002

United Nations (2019). Political declaration of the high-level meeting on universal health coverage, Seventy-fourth session Agenda item 126 Global health and foreign policy. Available at: https://documents-dds-ny.un.org/doc/UNDOC/GEN/N19/311/84/PDF/N1931184.pdf?OpenElement

[access: 07/01/2022]

United Nations (2022). Addressing the challenges of persons living with a rare disease and their families Seventy-sixth session Agenda item 28 Social development Resolution adopted by the General Assembly on 16 December 2021. Available at: https://www.rarediseasesinternational.org/wp-content/uploads/2022/01/Final-UN-Text-UN-Resolution-on-Persons-Living-with-a-Rare-Disease-and-their-Families.pdf

[access: 07/01/2022]

Varni, J. W., Seid, M., & Kurtin, P. S. (2001). PedsQL™ 4.0: Reliability and validity of the Pediatric Quality of Life Inventory™ Version 4.0 Generic Core Scales in healthy and patient populations. Medical care, 800-812. https://doi.org/10.1097/00005650-200108000-00006

von der Lippe, C., Neteland, I., & Feragen, K. B. (2022). Children with a rare congenital genetic disorder: A systematic review of parent experiences. Orphanet Journal of Rare Diseases, 17, 375. https://doi.org/10.1186/s13023-022-02525-0

Wakap, S., Lambert, D. M., Olry, A., Rodwell, C., Gueydan, C., Lanneau, V., ... & Rath, A. (2020). Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. European Journal of Human Genetics, 28(2), 165-173. https://doi.org/10.1038/s41431-019-0508-0

Westergaard, D., Moseley, P., Sørup, F. K. H., Baldi, P., & Brunak, S. (2019). Population-wide analysis of differences in disease progression patterns in men and women. Nature communications, 10(1), 1-14. https://doi.org/10.1038/s41467-019-08475-9

Wetterauer, B., & Schuster, R. (2008). Seltene Krankheiten. Bundesgesundheitsbl. 51, 519–528. https://doi.org/10.1007/s00103-008-0524-7

Witt, S., Bloemeke, J., Bullinger, M., Dingemann, J., Dellenmark-Blom, M., & Quitmann, J. (2019a). Agreement between mothers’, fathers’, and children’s ratings on health-related quality of life in children born with esophageal atresia–a German cross-sectional study. BMC pediatrics, 19(1), 1-9. https://doi.org/10.1186/s12887-019-1701-6

Witt, S., Kolb, B., Bloemeke, J., Mohnike, K., Bullinger, M., & Quitmann, J. (2019). Quality of life of children with achondroplasia and their parents-a German cross-sectional study. Orphanet journal of rare diseases, 14(1), 1-9. https://doi.org/10.1186/s13023-019-1171-9

World Health Organization Quality of Life Group (1995). The World Health Organization quality of life assessment (WHOQOL): position paper from the World Health Organization. Social science & medicine, 41(10), 1403-1409. https://doi.org/10.1016/0277-9536(95)00112-k

World Health Organization. International Statistical Classification of Diseases and Related Health Problems 11th Revision. Version for 2022. Available at: https://www.who.int/standards/classifications/frequently-asked-questions/rare-diseases

[access: 07/11/2022]

Wu, Y., Al-Janabi, H., Mallett, A., Quinlan, C., Schefe, I. E., Howell, K. B., Christodoulou, J., Leventer, R. J., Lockhart, P. J., Stark, Z., Boughtwood, T., & Goranitis. Parental health spillover effects of pediatric rare genetic conditions. Quality of Life Research, 29(9), 2445-2454. https://doi.org/10.1007/s11136-020-02497-3

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