Hyperphagia severity is underestimated in adults with Bardet-Biedl syndrome - a mixed-method cross-sectional study in...

Bardet-Biedl syndrome (BBS) is a rare genetic disease caused by primary ciliary dysfunction leading to retinal degeneration, rod-cone dystrophy, polydactyly, hyperphagia, early-onset obesity, renal dysfunction, hypogonadism, and learning difficulties. Hyperphagia, a pathological insatiable hunger leading to excessive and unusual food intake and persistent, obsessive food-seeking behaviours, is a frequent symptom associated with BBS. This study assessed hyperphagia severity in adults with BBS living in the UK, using a standard structured questionnaire accompanied by an in-depth semi-structured interview.

This non-interventional, cross-sectional study included 51 adults with BBS (49.0% males; 56.9% aged 18-34 years; mean [SD] body mass index [) BMI] of 36.5 [8.8] kg/m² [range 21.8-59.6]). Participants were excluded if they were currently prescribed or had previously taken setmelanotide. Most were of White ethnicity (82.4%), and age at diagnosis ranged from birth to 50 years. Participants completed a 14-item hyperphagia questionnaire comprising multiple-choice and open-ended questions; a subset (n=15) participated in semi-structured interviews. Interview transcripts were coded systematically by a qualitative researcher and reviewed with a BBS clinical expert to assign severity ratings. Semi-structured interviews were designed to address known limitations of self-reporting in this population, including the disability paradox, stigma, and cognitive difficulties.

Questionnaire data classified hyperphagia as severe in 5.9% (3/51) of participants, moderate in 45.1% (23/51), and mild in 49.0% (25/51), whereas semi-structured interviews classified hyperphagia as severe in 66.7% (10/15) participants, moderate in 26.7% (4/15), and mild in 6.7% (1/15). Notably, 86.7% (13/15) participants were assigned a higher severity level via interviews than questionnaires, while only two participants had the same classification across both methods. In a sub-analysis of participants with BMI ≥30 kg/m² (n=39), semi-structured interviews classified hyperphagia as severe in 69.2% (9/13) and moderate in 30.8% (4/13); none were classified as mild hyperphagia.

This study reveals a high prevalence of severe hyperphagia in adults with BBS based on semi-structured interviews and highlights substantial underreporting of hyperphagia severity when relying on self-reported questionnaires alone. The findings support incorporating semi-structured interviews as a mixed-method approach to provide a more comprehensive assessment of hyperphagia burden in adults with BBS.