Assessing Olfactory Acuity in Primary Ciliary Dyskinesia with the RSPH4A Founder Mutation

Background: /Objectives: Primary Ciliary Dyskinesia (PCD) is a rare genetic condition characterized by compromised mucociliary clearance and chronic respiratory manifestations. Anosmia, or the loss of smell, is a lesser-known but clinically relevant symptom that can significantly impact patient safety, nutritional status, and overall quality of life. The RSPH4A (c.921+3_921+6delAAGT) founder mutation is highly prevalent among Puerto Rican individuals with PCD and may carry distinct phenotypic implications. This study aimed to evaluate olfactory function in Puerto Rican PCD patients with this mutation using the Brief Smell Identification Test (BSIT) and to assess associations with age and sex. Methods: We conducted a case-control study involving 30 participants: 15 PCD patients with genetically confirmed RSPH4A mutations and 15 age- and sex-matched healthy controls. All participants completed the BSIT, and BSIT scores were compared by diagnosis, sex, and age. Results: PCD patients had significantly lower BSIT scores than controls (p = 0.0015). When stratified by sex, both male (p = 0.0289) and female (p = 0.0178) PCD patients demonstrated significantly lower BSIT scores compared to their respective healthy counterparts. Regression analysis showed a significant inverse correlation between age and BSIT score in the PCD group (r² = 0.2873, p = 0.0395), while no such relationship was observed in controls (r² = 0.0096, p = 0.7283). Among PCD patients, age-related decline in olfactory function was more pronounced in females (r² = 0.71, p = 0.005) than in males (r² = 0.31, p = 0.25). Conclusions: These findings demonstrate that the RSPH4A founder mutation is associated with measurable olfactory impairment in PCD patients, particularly in females and with advancing age. Routine assessment of olfactory function should be considered in the clinical evaluation of patients with PCD, as anosmia may represent a key phenotypic feature and contribute to disease burden.