The lungs in Alström syndrome: a retrospective analysis

Background Alström syndrome (AS) is a rare multisystemic disorder frequently associated with respiratory complications, which are a major cause of premature death. While fibrosis in multiple organs has been historically suggested as a hallmark of AS, including the lungs, definitive evidence in adult patients remains limited. Methods We conducted a retrospective study of adult patients diagnosed as AS seen in our National Multidisciplianry AS clinic from 2010 to 2024. Lung function test and high-resolution computed tomography (HRCT) of the thorax was performed in a subset of patients. Postmortem lung tissue analysis was available from four patients. Findings A total of 25/41 (61%) of the patients were unable to complete full lung function testing. Among those who did, 67% exhibited reduced lung volumes, with 47% showing decreased diffusing capacity of the lung for carbon monoxide but normal or elevated transfer coefficient for carbon monoxide, indicating extrapulmonary restrictive physiology. HRCT scans in 39 patients showed no evidence of diffuse interstitial lung fibrosis; however, breathing artefacts were common. Historical infantile cardiomyopathy was identified as a risk factor for adult pulmonary dysfunction. Post-mortem pathology reports were obtained from four patients and no diffuse fibrosis in the lung tissue was identified in any of the patients. Pulmonary hypertension and Acute Respiratory Distress Syndrome were identified as potential causes of respiratory morbidity and mortality, despite the absence of intrinsic interstitial lung disease. Interpretation This is the first large cohort study to depict the lung in adult patients with AS. This study provides no evidence for diffuse interstitial lung fibrosis in adult patients with AS, challenging prior assumptions. Pulmonary dysfunction appears mainly due to extrapulmonary restrictive physiology, with infantile cardiomyopathy as a possible risk factor. Pulmonary hypertension and acute respiratory distress syndrome, rather than intrinsic lung disease, likely underlie respiratory morbidity and mortality, highlighting the need for focused cardiopulmonary care. Although this study represents one of the largest single-centre cohorts of patients with AS reported to date, the overall sample size remains limited due to the ultra-rare nature of the disease and findings should be interpreted with caution. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.