Abstract
Cutaneous-skeletal hypophosphatemia syndrome (CSHS) is a rare inherited disorder that causes bone abnormalities due to hypophosphatemic rickets, which is a significant health comorbidity. Conventional therapy involving multiple daily oral doses of phosphate and calcitriol for CSHS rickets has limited effectiveness. We present the clinical features and therapeutic outcomes of the first Chinese child with bone fractures, a seizure history, and novel recurrent gastrointestinal manifestations of CSHS, including diarrhea and bowel obstruction. The effectiveness of conventional therapy and anti-FGF-23 antibody (burosumab) was evaluated. High-throughput DNA sequencing was performed on the patient's blood DNA, skin tissue, oral mucosa, and hair follicles to identify causative mutations. The child had a tissue-differentiated somatic activating HRAS p.G13R mutation. Burosumab resulted in a steady increase in blood phosphorus levels and a significant improvement in the patient's clinical symptoms and physical function compared to conventional phosphate therapy. It is suggested that younger children may receive a higher initial dosage of burosumab for better outcomes. However, long-term follow-up is still necessary to confirm its efficacy and safety.