Abstract
Purpose
Familial dysautonomia (FD) is a rare hereditary sensory and autonomic neuropathy (HSAN-3) that is clinically characterized by impaired pain and temperature perception and abnormal autonomic function. Patients with FD have gastrointestinal dysmotility and report a range of gastrointestinal symptoms that have yet to be systematically evaluated. The aim of this study was to establish the frequency and severity of gastrointestinal symptoms in patients with FD.
Methods
The validated National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) survey questionnaire, together with additional FD-specific questions, were distributed to 202 living patients with genetically confirmed FD who had been identified from the New York University FD Patient Registry or, when relevant, to their respective caretaker. As a comparison group, we used a general US adult population for whom PROMIS scores were available (N = 71,812).
Results
Of the 202 questionnaires distributed, 77 (38%) were returned, of which 53% were completed by the patient. Median age of the respondents was 25 years, and 44% were male. Gastrostomy tube was the sole nutrition route for 25% of the patients, while 53% were reliant on the gastrostomy tube only for liquid intake. The prevalence of gastrointestinal symptoms was significantly higher in each of the eight domains of PROMIS in patients with FD than in the controls. Gastrointestinal symptoms as measured by raw scores on the PROMIS scale were significantly less severe in the FD patient group than in the control population in all domains with the exception of the abdominal pain domain. The surveys completed by caregivers reported the same burden of symptoms as those completed only by patients.
Conclusion
Gastrointestinal symptoms affect nearly all patients with FD. Gastrointestinal symptoms are more prevalent in adult patients with FD than in the average US adult population but are less severe in the former.
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Acknowledgements
We thank Chris Almario for providing data for our reference study population.
Funding
This research was supported by National Institute of Neurological Disorders and Stroke (NINDS) grant U54NS065736 and the Familial Dysautonomia Foundation.
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J.-A. Palma has received fees as consultant or advisory board member for Lundbeck, Takeda, Biogen, Dr. Reddy’s, and PTC; is the principal investigator in clinical studies sponsored by Theravance, Biohaven, and Biogen; receives research support from the National Institutes of Health, the Food and Drug Administration, the Familial Dysautonomia Foundation, Inc., the MSA Coalition, and the Michael J. Fox Foundation; and is managing editor of Clinical Autonomic Research. L. Norcliffe-Kaufmann has received fees as consultant or advisory board member for PTC and Theravance; receives research support from the National Institutes of Health, the Food and Drug Administration, the Familial Dysautonomia Foundation, and the Michael J. Fox Foundation. H. Kaufmann serves on a scientific advisory board for Lundbeck, Biogen, Theravance, Biohaven, and PTC; receives research support from the National Institutes of Health, the Food and Drug Administration, the Familial Dysautonomia Foundation, Inc., the MSA Coalition, and the Michael J. Fox Foundation; and serves as Editor-in-Chief of Clinical Autonomic Research. A. Khan is a consultant for Medtronic. All other authors have no conflicts of interest to report.
Ethical approval
Patient consent was obtained following local Institutional Review Board (IRB) guidelines for recruiting research study participants when their capacity to given written informed consent was questionable. The study protocol was approved by the NYU School of Medicine IRB which received a copy of all questions. The study was conducted according to the guidelines laid down by the Helsinki Declaration of 1964, and its later amendments.
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Ramprasad, C., Norcliffe-Kaufmann, L., Palma, JA. et al. Frequency and burden of gastrointestinal symptoms in familial dysautonomia. Clin Auton Res 31, 109–116 (2021). https://doi.org/10.1007/s10286-020-00735-9
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DOI: https://doi.org/10.1007/s10286-020-00735-9