Telomeropathies and Our Experience: A Case Series

RM. Subbaiah1, Vinod Gunasekaran2, Thinaker Mani3

1Consultant Clinical Haematologist, Kauvery Hospital, Trichy, Tamilnadu, India

2Consultant Paediatric Haematologist, Kauvery Hospital, Trichy, Tamilnadu, India

3Consultant Gastroenterologist, Kauvery Hospital, Trichy, Tamilnadu, India



Telomere is a region with repetitive nucleotide sequences at each end of a chromosome, which protects the end of the chromosome from deterioration. Progressive shortening of telomeres leads to senescence, apoptosis or oncogenic transformation of somatic cells. Inherited conditions caused by genetic defects in the telomere maintenance machinery are called telomeropathies [1]. Symptoms of these disorders are extensive and may include features of bone marrow failure, pulmonary fibrosis, liver disease, skin/mucosal pigmentary abnormalities and cancer predisposition [2].

Case Presentation

Case 1

A 41-years-old female, unmarried, born out of a non-consanguineous marriage, was managed a year ago in Sep 2019 by medical gastroenterologist for massive hematemesis. She was then found to have chronic liver disease and portal hypertension. She required two sessions of endoscopic variceal ligation (EVL) to prevent further bleed. On follow up in Jan 2020, she had progressive pancytopenia for which hematology unit consultation was sought. Physical examination revealed icterus and mild splenomegaly. She had an inappropriately low reticulocyte count, moderate leukopenia and severe thrombocytopenia. Autoimmune work up for CLD in a young female turned out to be negative. Bone marrow showed a hypocellular marrow with reduction in trilineage haemopoiesis consistent with evolving aplasia. Cytogenetics was normal. NGS inherited bone marrow failure disorders ordered revealed a TERT mutation consistent with a “Telomeropathy”.

She is no on regular follow up, no further bleeding as of now. Cautiously low dose androgen was introduced to enhance failing hemopoiesis. Need for a liver and bone marrow transplantation under a very high risk was explained which the family denied.

Case 2

A 32-years-old male was found to have mild thrombocytopenia during routine health checkup a year ago. A year later he had exertional fatigue but no weight or appetite loss. Physical examination was unremarkable and showed no obvious external congenital malformation. Laboratory evaluation revealed pancytopenia with a low reticulocyte count. Bone marrow was markedly hypocellular and consistent with aplastic anemia. Cytogenetics revealed a complex karyotype. In view of young age, complex cytogenetics, NGS for inherited bone marrow failure disorders ordered revealed RTEL mutation which is again a telomeropathy. He has no siblings and hence matched unrelated donor search was recommended for an allogeneic stem cell transplantation.

Case 3

A 24-years-old female was found to have pancytopenia in Aug 2019 during pregnancy. Bone marrow examination done at a tertiary care centre revealed aplastic anemia. Cytogenetics was normal and stress Cytogenetics did not reveal any increased sensitivity to Mitomycin C. She was managed with transfusions, Cyclosporine and Eltrombopag since then. Post-delivery until now she required intermittent blood transfusions to keep herself asymptomatic. She reported no undue bleeding. Her blood counts started showing a decreasing trend. Physical examination at another tertiary care centre revealed pallor, reticulated pigmentation over hands, feet. Oral examination revealed leukoplakia and hyperpigmentation. Nails showed dystrophy. This mucocutaneous triad (abnormal reticulated skin pigmentation, oral leukoplakia and nail dystrophy) is characteristic of an inherited bone marrow failure syndrome called dyskeratosis congenita (DKC). Bone marrow repeated revealed aplastic anemia however no dysplasia. Mutation panel by NGS for inherited bone marrow failure syndrome revealed a WRAP53 mutation. Hence telomeropathy was considered. She had no pulmonary involvement as of now clinically. Her younger brother was not HLA matched with her. She was started on low dose androgen Danazol. In case of worsening, only an allogeneic BMT would save her from hematopathology component but not pulmonary or liver pathology.


Telomeropathies have to be considered when a bone marrow failure is associated with pulmonary or liver fibrotic pathology or any other associations reported. Early diagnosis is crucial in reducing morbidity or mortality. Danazol enhances hemopoiesis [3]. Stem cell transplantation may correct the hematopathology but no other system pathology [4],


  • Holohan B, Wright WE, Shay JW. Telomeropathies: An emerging spectrum disorder. J Cell Biol 2014;205(3):289-99.
  • Townsley DM, Dumitriu B, Young NS. Bone marrow failure and the telomeropathies. Blood. 2014;124(18):2775-83.
  • Townsley DM, Dumitriu B, Liu D, Biancotto A, Weinstein B, Chen C, et al. Danazol treatment for telomere diseases. New Engl J Med. 2016;374(20):1922-31.
  • Armando RG, Mengual Gomez DL, Maggio J, Sanmartin MC, Gomez DE. Telomeropathies: Etiology, diagnosis, treatment and follow-up. Ethical and legal considerations. Clin Gen. 2019;96(1):3-16.