Clinical profile of patients with Interstitial Lung Disease (ILD) and Telomere Biology Disorder (TBD): A single-center retrospective experience

<bold>Background:</bold> Adults with TBD have abnormally short telomeres produced by pathogenic mutations in telomerase genes, presenting with multisystemic disease frequently associated with ILD. <bold>Objective and methods:</bold> Medical record of patients with diagnosed ILD and suspected TBD, evaluated at an ILD center between 2022-2024 were analysed. Flow-FISH analysis was used to identify Telomere Length (TL). <bold>Results:</bold> Thirteen individuals were included with mean age of 63.7 years; 61% with smoking history and 61% with familial ILD. Common manifestations were cough and dyspnea (92.3%), macrocytosis (54%), early greying of hair (30.8%), hepatic fibrosis (23%); probable UIP pattern on imaging (38.5%), mild to moderate restrictive spirometry (77%) and DLCO (69.2%) abnormality. Over 77% had progressing fibrosis. Six patients (46.2%) had TL for both lymphocyte and granulocyte below 1 percentile, while 30.8% (n = 4) had TL for lymphocytes in the 1st-10th percentile and granulocyte TL below 1 percentile. Three (23.1%) individuals had lymphocyte TL in 10th-50th percentile with granulocyte TL below 1 percentile. <bold>Conclusion:</bold> Patients with TBD have an aggressive ILD course. Interestingly, 3 individuals with lymphocyte TL between 50th and 10th percentile-despite having granulocyte TL less than 1 percentile-are not classically considered diagnostic for TBD. They had progressive ILD, phenotypic features of TBD (early hair greying, macrocytosis), presence of VUS on TERT gene with familial IPF in one patient; indicating granulocyte TL less than 1 percentile may have clinical significance in the setting of pulmonary fibrosis, warranting corroboration with larger prospective studies.