A Military Veteran with Pulmonary Fibrosis, Hepatic Cirrhosis, Bone Marrow Dysfunction and Shortened Telomeres Found to Have GAVE, a Potential Unsuspected Consequence of Telomere Spectrum Disorder.

Background

Telomeres are repetitive DNA sequences at chromosome ends that maintain genomic stability and shorten with age. Mutations in genes such as DKC1, TERC, TERT, NOP10, TINF2 and NHP2 cause Telomere Spectrum Disorders (TSD), leading to shortened telomeres. Acquired TSDs arise from environmental or occupational exposures and commonly affect veterans, truck drivers, and industrial workers. These exposures generate reactive oxygen species associated with cancer, liver disease, pulmonary disease, and bone marrow complications. Idiopathic Pulmonary Fibrosis (IPF) is most common pulmonary manifestation, followed by hepatic fibrosis/cirrhosis, hematologic disorders (e.g., aplastic anemia, MDS), and rarely gastrointestinal findings. This case describes a Gulf War veteran with suspected acquired short telomeres and multisystem involvement (idiopathic cirrhosis, pulmonary fibrosis, cytopenias) and uniquely found to have gastrointestinal (Gastric Antral Vascular Ectasia, GAVE), a potential unsuspected manifestation of TSD. Methods/Case: A 76-year-old male with atrial fibrillation (post-Watchman), cryptogenic cirrhosis, COPD, IPF, diabetes, and anemia presented with severe shortness of breath and hypoxia. Admitted for Sepsis and Acute Hypoxic Respiratory Failure. Treated with AVAPS, IV Zosyn, IV Lasix, steroids, bronchodilators, and diuretics. His condition improved, and he was discharged on baseline 3L O2. His Gl history included GAVE, an unsuspected bleeding complication causing chronic iron-deficiency anemia. Hematologic findings included chronic anemia, thrombocytopenia, and a hypocellular bone marrow with 12% atypical NK cells. Discussion/

Results

The patient's Gulf War exposure to oil fire pollutants (benzene, toluene, PAHs, lead, cadmium, and particulate matter) likely contributed to telomere shortening and TSD-related multisystem disease. Given his shortened telomeres, testing for TERC and TERT mutations is warranted. GAVE ("watermelon stomach") is a rare cause of GI bleeding characterized by dilated gastric vessels and chronic anemia and has been linked to TSD but no current reports have documented this association. Its occurrence in this patient suggests an unrecognized gastrointestinal manifestation of TSD as the patient does not have known history of portal hypertension.

Conclusions

This represents an potentially underreported manifestation of acquired TSD presenting with combined hepatic, pulmonary, hematologic, and gastrointestinal (GAVE) involvement.