SUN-724 Fracture And Bone Fragility In Glass Syndrome: A Case Report

Abstract Disclosure: F. Abdo: None. M. Barreiro: None. G. Aekta: None. SATB2-Associated Syndrome (Glass Syndrome) is a rare genetic disorder resulting from mutations in the SATB2 gene, characterized by neurodevelopmental delay, craniofacial anomalies, osteoporosis, and recurrent fractures. It is traditionally classified as a neurodevelopmental disorder, but it has a significant bone implication due to the SATB2 gene effect on osteoblast differentiation and bone formation. A 31-year-old female with a history of neurodevelopmental delay referred to endocrinology for persistently elevated alkaline phosphatase (ALP) ranging from 160-210 U/L. She has a history of limited verbal communication, mild scoliosis, and multiple fragility fractures requiring surgeries: the first fracture occurred during infancy, and most recent fractures involving the left femur, pelvic bone, and right clavicle sp ORIF. Her medications include oral contraceptive pills, and intermittent calcium and vitamin D supplementation.Her exam revealed dolichocephaly, facial dysmorphism, poor dentition, valgus deformity of bilateral the legs, and scoliosis. Laboratory findings were notable for normal GGT, bilirubin, ALT, AST, corrected calcium 9.5 mg/dL, phosphorus 2.7 mg/dL, PTH 14 pg/mL [18.5-88 pg/mL], 25-hydroxy vitamin D 61 ng/mL, and 1,25-dihydroxy vitamin D 93 pg/mL. Bone-specific ALP was elevated at 56 U/L, and C-telopeptide was elevated at 400s [136-689 pg/mL in premenopausal women], indicating high bone turnover. DEXA scan revealed a Z-score of -3.8 in the spine and -2.5 in the right total femur.Osteogenesis Imperfecta, is the main differential that causes frequent fractures from infancy, alkaline phosphatase can be normal or elevated, but she lacked the phenotypic features. This will eventually be ruled out via genetic testing. Other differentials include osteomalacia, but she did not have longstanding vitamin D or calcium deficiency. Lastly, bone disease due to hypophosphatasia is associated with low ALP.Genetic testing was done and showed SATB2 gene mutation, consistent with Glass Syndrome. SATB2 gene influences osteoblast differentiation and matrix formation through the modulation of expression and function of osteoblast-specific genes. Disruption of SATB2 function impairs bone remodeling and mineralization, leading to increased bone turnover, reduced bone density, high incidence of fractures. Common skeletal features include osteopenia, osteoporosis, progressive tibial bowing, scoliosis, and delayed bone age. Persistent elevation of bone-specific ALP with clinically significant pathologic fractures in the absence of other diagnosis should prompt investigation into genetic causes such as a SATB2 gene mutation. Management of such patients includes optimizing calcium and vitamin D levels, anti-resorptive therapy, and regular monitoring with DEXA scans. Genetic counseling and a multidisciplinary approach are essential for comprehensive care. Presentation: Sunday, July 13, 2025