Diagnosis and management of telomere biology disorders in developing countries

Telomere biology disorders (TBDs) have a heterogeneous presentation deepened by variable, age-dependent, multisystem manifestations. In low- and middle-income countries, delayed diagnosis is common due to limited access to confirmatory testing. As a result, diagnosis frequently relies on clinical pattern recognition by hematologists and geneticists. This review summarizes practical approaches to suspecting, evaluating, and managing TBDs in resource-constrained settings. We highlight pivotal clinical signs and "red flag" combinations that should strengthen the suspicion of a TBD, including persistent cytopenias, hypocellular bone marrow, mucocutaneous features, early-onset idiopathic pulmonary fibrosis, unexplained chronic liver disease, immunodeficiency, and early malignancy. We present pragmatic diagnostic algorithms when specialized tests are unavailable, emphasizing careful family history recording, thorough full-body examination, and use of basic laboratory test tools, such as serial complete blood counts (CBC), spirometry with diffusing capacity for carbon monoxide, and noninvasive hepatic assessment, for strong suspicion of TBDs. Current modalities for telomere length (TL) assessment are reviewed with attention to feasibility and limitations in LMICs, including Terminal Restriction Fragment analysis, quantitative PCR, Flow-fluorescence in situ hybridization, and emerging long-read sequencing approaches. Management requires structured, multidisciplinary surveillance for hematologic decline, detection of clonal evolution, pulmonary and hepatic complications, and cancer risk. We review implementable monitoring strategies and discuss key therapeutic considerations in LMICs, including androgen therapy as a widely applicable disease-modifying option and the substantial logistical barriers to hematopoietic stem cell transplantation, donor evaluation, and long-term follow-up. Resource-stratified care pathways and regional referral networks are essential to improve outcomes for patients with TBDs in developing countries.