Case Presentation: A 24-year-old male with a history of pancytopenia presented to the emergency department with generalized abdominal pain. One year prior, he started having intermittent mild abdominal pain which was attributed to irritable bowel disease. Three months prior, he developed a pruritic red rash on his arms and legs and intermittent bleeding from his gums while brushing. One month prior, he developed large ecchymosis on his bilateral arms and presented to another hospital where he was found to have a diffuse petechial rash on his extremities and pancytopenia. He did not have evidence of acute leukemia on bone marrow biopsy and was thought to have a bone marrow failure syndrome. He again presented to the hospital with acute worsening of his abdominal pain. His pain increased to 10/10 over the preceding three days with radiation to bilateral flanks. It was worse with movement and he noticed new swelling and firmness of his abdomen without nausea. On exam, he had gingival hyperplasia without active bleeding as well as diffuse abdominal tenderness and distension. His white blood cell count was 3.1K/uL, hemoglobin was 8.5g/dL, and platelet count was 58K/uL. His liver function tests were mildly elevated with an aspartate transaminase of 106 U/L, alanine transaminase of 60 U/L, alkaline phosphatase of 29 U/L, and total bilirubin of 3.5mg/dL. Abdominal ultrasound showed small volume ascites, and a diagnostic and therapeutic paracentesis was performed. His serum ascites albumin gradient was 1.6 and gram stain did not show any organisms. A trans-jugular liver biopsy showed a hepatic venous pressure gradient 29 mmHg (normal < 5), sinusoidal dilation with congestion consistent with venous outflow impairment, as well as extramedullary hematopoiesis. A hepatic venogram of the right hepatic vein showed concentric stenosis of the outflow of the hepatic veins contiguous with diffuse intrahepatic stenosis of the vena cava. Over the subsequent four months, he required increasingly frequent paracentesis and ultimately underwent a trans-jugular intrahepatic portosystemic shunt. With both bone marrow failure and cirrhosis in an otherwise healthy young patient, further testing was pursued and showed short telomeres across several cell lines, consistent with a telomere biology disorder.
Discussion: Telomeropathies are caused by genetic defects in telomere maintenance with a range of organ involvement including bone marrow, blood, skin, lungs and liver. In these disorders, it is thought that telomere shortening occurs throughout the body even in patients that only have one clinical manifestation and telomere pathology is closely related to organ failure and aging. As with our patient, these disorders can cause bone marrow failure and cirrhosis, although the affected organs vary significantly between patients. This patient did not have a family history consistent with a telomeropathy nor environmental exposures known to impact telomere maintenance such as air pollution or tobacco exposure.
Conclusions: A number of patients with telomeropathies may require hematopoietic stem cell transplantation for their bone marrow failure and identification of a telomeropathy can importantly prompt genetic screening of related donors. Additionally, affected patients are at increased risk of future malignancy, emphasizing the importance of close surveillance. A high level of suspicion is necessary for diagnosis and early onset of multiple organ failure should prompt consideration of an underlying disorder.