Telomeropatiler

Telomeropatiler refers to a group of rare, inherited disorders characterized by progressive telomere shortening. Telomeres are protective caps at the ends of chromosomes that shorten with each cell division. In telomeropathies, this shortening occurs at an accelerated rate, leading to premature cellular senescence and dysfunction in tissues with high cell turnover, such as the bone marrow, skin, and lungs.

The genetic basis for telomeropathies involves mutations in genes essential for telomere maintenance, including those encoding components of the telomerase enzyme complex (e.g., TERC, TERT, TERC), dyskerin, and other associated proteins. These mutations result in impaired telomere maintenance, leading to a spectrum of clinical manifestations.

Common symptoms include bone marrow failure, presenting as aplastic anemia, neutropenia, and thrombocytopenia. Skin manifestations can include dyskeratosis congenita, characterized by skin pigmentation abnormalities, oral leukoplakia, and nail dystrophy. Pulmonary fibrosis is another significant complication, leading to respiratory insufficiency. Other potential issues include gastrointestinal problems, liver disease, and an increased risk of developing certain cancers.

Diagnosis typically involves a combination of clinical evaluation, family history, and genetic testing to identify mutations in telomere maintenance genes. Telomere length analysis in peripheral blood leukocytes can also provide supporting evidence. Treatment is largely supportive, focusing on managing specific organ manifestations, such as blood transfusions for anemia, antibiotics for infections, and pulmonary support. In severe cases, hematopoietic stem cell transplantation may be considered for bone marrow failure. Research into novel therapeutic strategies targeting telomere biology is ongoing.