Patient experience informing outcomes and research in rare disease: Citrin deficiency as a case study

We are pleased to announce the publication of a new paper titled “Patient Experience Informing Outcomes and Research in Rare Disease: Citrin Deficiency as a Case Study” in Molecular Genetics and Metabolism. This is the first study to explore the lived experiences of adults with citrin deficiency (CD). This research was conceived and conducted by the Citrin Foundation. We invite you to read the full publication linked here: https://doi.org/10.1016/j.ymgme.2026.110141

 

 

CD is described in the literature as having heterogeneous, age-dependent phenotypes, with the “silent” or “adaptive” period characterized as largely asymptomatic and no clear dominant features across phenotypes. This study examined whether published descriptions align with patients’ lived experiences, particularly whether the silent/adaptive period is asymptomatic and whether patients report consistent universal symptoms.

 

The Citrin Deficiency Adult Patient Experience Survey was conducted among seven adult CD patients who are registered members of the Foundation’s patient network. The survey content was developed deductively, informed by literature review and prior engagement with patients, caregivers, and clinicians. It assessed CD disease experience across multiple domains including symptoms, treatment, diet, research participation, daily functioning, and emotional well-being.

 

This in-depth survey was designed to be interviewer-administered with open-ended questions to generate rich qualitative data in an iterative manner with a small participant sample. This process culminated in a 64-item questionnaire that was self-administered by the final participant. Results were examined using a qualitative descriptive approach, with inductive content analysis to identify common domains of disease burden. Findings were then compared with published results and methods from other CD cohort studies.

 

Fatigue and symptoms triggered by excessive carbohydrate intake relative to individual tolerance levels were consistently reported by all participants and may represent universal symptoms. Participants reported not only an aversion to carbohydrates as described in existing literature, but also physiological responses to excessive carbohydrate intake, with symptoms such as nausea, vomiting, abdominal pain, and fatigue. These symptoms have not been systematically examined before. Other underrecognized disease domains included gastrointestinal symptoms, poor appetite, and psychological impacts.

 

Collectively, our findings suggest that the lived experiences of patients are not congruent with published literature, questioning the notion of an asymptomatic phase in CD and suggesting the presence of universal symptoms which warrant further studies.

 

While the small cohort (n=7) limits definitive conclusions and further validations in larger studies are needed and currently being planned, our findings may help to identify under-recognized disease domains that could inform the development of patient reported outcome measures (PROMs), clinical trial endpoints, research priorities, and future diagnostic and management approaches.

 

More broadly, this study also highlights how patient organization-led surveys can capture lived experiences of patients with rare diseases and uncover disease burdens that may be overlooked in conventional clinical assessments.

 

We extend our deepest thanks to all patients, families, and the professionals acknowledged in this study, especially the participants who made this work possible.

 

This paper is part of the Special Issue of the 6th International Symposium on Urea Cycle Disorders. We sincerely thank the committees of the 6th UCD Satellite Symposium for inviting us to publish this work.