Short telomere syndrome (STS) encompasses a broad family of genetically inherited conditions caused by various mutations in telomerase and other telomere maintenance genes, resulting in premature telomere shortening. STS involves a variety of clinical manifestations, including dyskeratosis congenita, premature achromotrichia, bone marrow failure, immunodeficiency, pulmonary fibrosis and liver disease. Liver histopathologic features in STS patients have not been well characterized. We report a 46-year-old male patient who presented for dyspnea. The patient had a complicated medical history significant for immune thrombocytopenic purpura and splenectomy, recurrent respiratory tract infections, pneumonia, primary immunodeficiency, and severe hepatopulmonary syndrome. He and his brother both developed gray hair by their late 20s. He had a long history of intermittently elevated liver enzymes starting at age 33. These clinical manifestations prompted an evaluation for a possible telomere biology disorder, which revealed the telomere length was critically short and fell at or below the first percentile for age, supporting the diagnosis. The liver biopsy showed marked portal inflammation with interface hepatitis, ductular reaction and frequent foci of lobular inflammation with focal hepatocyte dropout. Hepatocytes around the portal tracts demonstrated ballooning degeneration and occasional Mallory-Denk bodies. A trichrome stain highlighted bridging fibrosis. A literature review shows liver histology is available in only a small number of STS patients, demonstrating a variety of morphologic features. Our case and others suggest liver disease associated with STS exhibits a spectrum of histopathology. Being aware of these features is important for establishing the correct diagnosis of STS which is under recognized.
Clinical and molecular correlates from a predominantly adult cohort of patients with short telomere lengths
