Abstract
Congenital disorders of glycosylation (CDG) are ultra-rare diseases showing a great phenotypic diversity ranging from mono- to multi-organ/multisystem involvement. Liver involvement, mostly nonprogressive, is often reported in CDG patients. The main objectives of this work were (1) to better understand liver involvement in CDG patients through a liver electronic questionnaire targeting CDG families (LeQCDG) and (2) to compare responses from LeQCDG participants with literature review regarding the prevalence of liver disease and the occurrence of liver symptoms in CDG patients. The network of patient advocacy groups, families and professionals (CDG & Allies – PPAIN) developed the LeQCDG by adapting validated published questionnaires. The LeQCDG was approved by an ethics committee, and the recruitment of patients and caregivers proceeded through social media platforms. Participants were asked to report past or present liver-related symptoms (e.g. hepatomegaly, liver fibrosis and cirrhosis) and laboratory results (e.g. biochemical and/or radiological). From 11 December 2016 to 22 January 2017, 155 questionnaires were completed. Liver disease was present in 29.9% of CDG patients. Main symptoms reported included hepatomegaly, increased levels of serum transaminases, fibrosis, steatosis and cirrhosis. The data obtained in this online survey confirm findings from a recent literature review of 25 years of published evidence (r = 0.927, P = 0.02). Our questionnaire collected large amounts of meaningful, clinical and patient-oriented data in a short period of time without geographic limitations. Internet-based approaches are especially relevant in the context of ultra-rare diseases such as CDG.
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- CDG & Allies:
-
PPAIN – CDG Professionals and Patient Associations International Network
- CDG:
-
Congenital disorder(s) of glycosylation
- CLDQ:
-
Chronic liver disease questionnaire
- ePROs:
-
Electronic patient-reported outcomes
- HQLQ:
-
Hepatitis quality-of-life questionnaire
- LDQoL:
-
Liver disease quality-of-life questionnaire
- LDSI 2.0:
-
Liver disease symptom index 2.0
- LeQCDG:
-
Liver electronic questionnaire for CDG
- PLD-Q:
-
Polycystic liver disease-specific symptom questionnaire
- pLTQ:
-
Post-liver transplant quality of life
- PROs:
-
Patient-reported outcomes
- QoL:
-
Quality of life
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Acknowledgements
Dorinda Marques-da-Silva acknowledges the support from the Rare Disease Foundation’s microgrant and ‘Liliana Scientific Scholarship’; Rita Francisco acknowledges Fundação para a Ciência e Tecnologia for the grant SFRH/BD/124326/2016 awarded to her.
We also thank the CDG & Allies – Professionals and Patient Associations International Network (CDG & Allies PPAIN), whose network expertise greatly helped in the creation of this manuscript.
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Communicated by: Pascale de Lonlay
Synopsis
Liver involvement in CDG was accessed through a CDG family-targeted online questionnaire based on a recent literature review. Main symptoms reported included hepatomegaly, increased levels of serum transaminases, fibrosis, steatosis and cirrhosis. Electronic questionnaires can boost knowledge on rare diseases, improving possible treatments and management. This is also useful with regard to future clinical trials.
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Conflict of Interests
Vanessa dos Reis Ferreira is the president and founder of the Portuguese Association for CDG and other Rare Metabolic Diseases (APCDG-DMR). All other authors declare no competing financial interests.
Details of the Contributions of Individual Authors
Dorinda Marques-da-Silva participated in planning, conducted the work, analysed data, conceived the article outline, participated in the conception and design, drafted all the manuscript including figures and tables, obtained final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved.
Rita Francisco participated in conducting the work; conceiving the article outline, conception and design; and drafting the manuscript.
Vanessa dos Reis Ferreira participated in planning and conducting the work; conceiving the article outline, conception and design; and critically revising it for important intellectual content.
Liz Forbat participated in conception and design and in critically revising it for important intellectual content.
Ricardo Lagoa helped in conception and design, data analysis and drafting the tables and participated in critically revising the manuscript for important intellectual content.
Paula A. Videira participated in planning the work and the conception, design and revision of the literature and in critically revising it for important intellectual content.
Peter Witters participated in conception and design and in critically revising the manuscript for important intellectual content.
Jaak Jaeken conceived in planning the work and the article outline; participated in the conception, design and analysis of the article; and was involved in drafting the manuscript and critically revising it for important intellectual content.
David Cassiman participated in planning the work and conceiving the article outline and the conception, design and analysis of the article and was involved in drafting the manuscript and in critically revising it for important intellectual content. He is the guarantor of the article, accepts full responsibility for the work submitted and controlled the decision to publish.
All authors gave final approval of the version to be published.
Ethical Guidelines, Human and Animal Rights and Consents
This work has been carried out in accordance with The Code of Ethics of the World Medical Association. Ethical approval for this study was obtained from the Ethics Committee at the Faculty of Psychology, Lisbon University (20/07/2016). Besides, the informed consent was obtained from participants, and the privacy rights of human subjects were ensured.
Funding
Dorinda Marques-da-Silva acknowledges the support from the Rare Disease Foundation’s microgrant and ‘Liliana Scientific Scholarship’; Rita Francisco acknowledges Fundação para a Ciência e Tecnologia for the grant SFRH/BD/124326/2016 awarded to her.
The authors confirmed independence from the sponsors; the content of the article has not been influenced by sponsors.
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Marques-da-Silva, D. et al. (2018). An Electronic Questionnaire for Liver Assessment in Congenital Disorders of Glycosylation (LeQCDG): A Patient-Centered Study. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 44. JIMD Reports, vol 44. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2018_121
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DOI: https://doi.org/10.1007/8904_2018_121
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