Novel compound heterozygous ITGA2B mutations in Glanzmann thrombasthenia associated with adolescent osteoporosis.

Glanzmann thrombasthenia (GT), caused by defects in integrin αIIbβ3, is characterized by impaired platelet aggregation. While αIIbβ3 dysfunction is well-documented in hematologic pathology, its association with bone metabolism remains controversial. Here, we report a 14-year-old GT patient with a novel compound heterozygous mutation in ITGA2B (Arg358His and Leu466Pro) and asymptomatic radial osteoporosis. Platelet aggregation assays and flow cytometry confirmed type I GT with severely reduced CD41/CD61 expression (<5%). Structural modeling revealed that both mutations destabilize the β-propeller domain of αIIb, leading to protein degradation. Notably, dual-energy X-ray absorptiometry demonstrated osteoporosis, despite the absence of secondary causes. This case expands the genotypic spectrum of GT and provides clinical evidence linking ITGA2B mutations to abnormal bone metabolism.