Significant improvement following intravenous zoledronate therapy in Bruck syndrome 2 due to a rare PLOD2 gene variant

Bruck syndrome (BRKS), an uncommon variant of osteogenesis imperfecta, is a rare autosomal recessive bone mineral disease characterized by an infantile onset of recurrent fragility fractures. Mutations in FKBP10 and PLOD2 genes cause BRKS1 and BRKS2, respectively. PLOD2 encodes lysyl hydroxylase 2 (LH2), which is pivotal in forming collagen cross-linkages to form mature bone. This case describes a 4-year-3-month-old girl who was found to have her first fragility fracture within 1 month of age. With four more fragility fractures within 2 years of age, she was diagnosed with osteogenesis imperfecta type IV initially. On examination, she was found to have short stature (length Z-score −2.69) and fixed extension and flexion deformities of the hip and knee joints, respectively. In the absence of abnormal biochemical skeletal parameters, whole-exome sequencing identified a PLOD2 mutation in exon 18. Threonine was substituted for isoleucine at codon 629 of exon 18, which was reported only once among approximately 20 mutations in the PLOD2 gene. She was initially treated with intravenous zoledronate (0.025 mg/kg) and received repeated doses every 6 months. She remained fracture-free during the therapy. Our case highlights the initial diagnostic dilemmas encountered in evaluating an infant-onset recurrent fragility fractures and gradual bony deformities.