The hidden burden of AATD: High prevalence of emotional distress and the ‘care gap’ in mental health support

BACKGROUND: :Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder mainly affecting the lungs and liver, but its psychological, functional, and relational burden remains insufficiently characterizedcharacterised. OBJECTIVE: To describe emotional distress, health-related quality of life, interpersonal and sexual difficulties, and daily functional limitations in individuals with AATD. METHODS: We conducted a cross-sectional online survey in Italy between October and December 2025 among individuals with AATD. Socio-demographic, clinical, and psychosocial data were collected using an ad hoc questionnaire, the Hospital Anxiety and Depression Scale (HADS), and the 12-item Short Form Health Survey (SF-12). HADS subscales were reconstructed from item-level responses, applying reverse scoring where appropriate. RESULTS: The study included 130 participants (mean age 56.3 ± 13.5 years; 53.8% female). Pulmonary involvement was the most frequent manifestation (68.5%). Disease-related limitations were reported in daily functioning by 57.7% and in social participation by 53.1%. Clinically significant symptoms were present in 46.2% for anxiety and 17.7% for depression. The SF-12-derived ad hoc unweighted physical and mental descriptive composites were 56.68 ± 27.47 and 54.53 ± 26.91. Women reported higher anxiety and poorer mental-composite scores, while participants receiving augmentation therapy showed worse depressive and perceived-health burden. Sexual-life changes were reported by 37/96 partnered participants (38.5%). Fifteen of 128 respondents (11.7%; two preferred not to answer) reported current psychological support. In exploratory covariate-adjusted models, functional and perceived-health correlates remained associated with clinically significant anxiety. CONCLUSIONS: In this cross-sectional survey, respondents with AATD reported substantial emotional, functional, and relational burden, while few were receiving psychological support. The self-selected sample and absence of a non-AATD comparison group preclude causal or disease-specific inference; the findings support evaluation of brief psychological screening and defined referral pathways in multidisciplinary AATD care.