S5709 Liver Cirrhosis and Interstitial Lung Disease in Short Telomere Syndrome: A Case Highlighting the Importance of Early Detection and Transplant Candidacy Challenges

Introduction: Short telomere syndrome (STS) is a rare, inherited disorder caused by mutations in telomere maintenance genes, leading to progressive multiorgan dysfunction. Common features include pulmonary fibrosis, bone marrow failure, and cirrhosis. Due to its heterogeneity, diagnosis is often delayed. We present a case of a 57-year-old man with STS and interstitial lung disease (ILD), evaluated for combined lung-liver transplantation. Case Description/Methods: A 57-year-old man with ILD and cryptogenic cirrhosis complicated by Grade 3 esophageal varices (s/p banding 2/2023), ascites, hepatic encephalopathy, and hepatopulmonary syndrome presented with fever, abdominal distension, and melena. Labs: platelets 88,000, hemoglobin 6.7 g/dL, international normalized ratio 1.7, total bilirubin 4.4 mg/dL. Computed tomography showed extensive fibrosis with subpleural reticular and ground-glass opacities, traction bronchiectasis, and architectural distortion, basilar and peripheral. Genetic testing confirmed STS with critically short telomeres (lymphocytes 1%–10%, granulocytes <1%). He was started on prednisone for suspected ILD flare and empiric antibiotics, and transferred for lung-liver transplant evaluation. During workup, he developed progressive respiratory failure and died from rapid deterioration. Autopsy showed bilateral lung diffuse interstitial fibrosis with repair, focal pneumonia and hemorrhage, right lower lung lobe subpleural scarring, and bilateral lungs focal petechial hemorrhages, liver diffuse fibrosis with surface nodularity, normocellular bone marrow with Megakaryocyte hypoplasia, and cardiomegaly with bilateral atrial enlargement and ventricular moderate interstitial fibrosis. Discussion: STS is a rare, autosomal dominant disorder with highly variable clinical expression. Its presentation often overlaps with other more common diseases, leading to underdiagnosis or delayed recognition. Pulmonary disease is the most common manifestation and liver transplant is essential for survival. This case illustrates the aggressive and multisystem progression of STS and the critical importance of early suspicion, diagnosis, and referral—especially for transplant eligibility. Genetic testing and telomere length analysis are essential for confirmation. Additionally, due to genetic anticipation, early family screening and counseling are warranted. The case underscores the need for standardized protocols for early recognition, transplant timing, and comprehensive multidisciplinary management.