Endocrine Abstracts

JOINT3466

Introduction: X-linked dominant hypophosphatemic rickets (XLH) is a rare hereditary disorder characterized by chronic progressive phosphate wasting due to excessive fibroblast growth factor 23 (FGF23) activity. This condition typically manifests with delayed motor development, gait abnormalities, progressive skeletal deformities, lower limb pain, impaired growth, craniosynostosis, dental abscesses, and hypotonia. Biochemically, it presents with hypophosphatemia, elevated alkaline phosphatase (ALP), and a reduced tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR). Radiographic findings include widened growth plates in both upper and lower limbs, reflecting severe rickets-related skeletal abnormalities.

Case Report: We present the case of a Kazakh girl born in 2017, who was admitted to the pediatric endocrinology department with complaints of lower limb deformities, gait disturbances, and shin pain during prolonged walking. Clinical examination revealed significant growth retardation, severe varus deformity of the lower limbs, hypertelorism, and multiple dental caries. Additional phenotypic characteristics included an antimongoloid slant of the eyes, a flat nasal bridge, and a prominent forehead. Renal ultrasound detected bilateral nephromegaly, while radiographic imaging confirmed severe lower limb deformities, cortical thinning, and metaphyseal irregularities in both upper and lower limbs. The severity of rickets was assessed as 2 points out of 5 on the Radiographic Severity Score (RSS) scale. Genetic analysis through whole-genome sequencing identified a heterozygous deletion on the X chromosome (chrX:22202815-22216826) encompassing 16 exons of the PHEX gene (NM000444.6), confirming a pathogenic variant associated with XLH. Biochemical analysis further demonstrated disturbances in phosphorus metabolism, including elevated ALP 522.90 U/l (82.00 - 383.00), hypophosphatemia 0.85 mmol/l (0.95 - 1.85), increased urinary phosphorus excretion, and decreased TmP/GFR 0.71 mmol/l (1.15 - 2.6).

Conclusion: The patient was diagnosed with X-linked dominant hypophosphatemic rickets based on clinical, biochemical, genetic, and imaging findings. Targeted therapy with burosumab (Crivit) was initiated at a dose of 0.8 mg/kg subcutaneously every two weeks. This case highlights the importance of early genetic testing, comprehensive metabolic evaluation, and targeted treatment in improving outcomes for patients with XLH.