Abstract
Abstract Introduction X-linked hypophosphataemic rickets (XLH) is a rare hereditary disease caused by pathogenic mutations in the PHEX gene. It causes chronic hypophosphataemia and abnormal mineralisation of the bones, resulting in progressive skeletal deformity. XLH can be diagnosed in affected individuals early in the course of their disease. However, in some patients, diagnosis is delayed until adulthood, leading to poor functional outcomes. Case presentation We present a 23-year-old male patient with severe skeletal deformities, inability to walk independently, chronic lower limb pain, joint contractures, short stature, and premature tooth loss. Symptoms had been present since birth. During childhood, the patient was repeatedly treated for nutritional rickets without any clinical improvement. On physical examination: height—132 cm, body weight—54 kg, marked deformities of the upper and lower limbs, bilateral genu valgum, thoracic scoliosis, and severe functional limitation were observed, requiring wheelchair assistance. The patient had persistent hypophosphataemia (0.61-0.77 mmol/L), normal total serum calcium levels (2.23-2.32 mmol/L) and slightly decreased vitamin D levels (29.4 ng/mL). Alkaline phosphatase activity (ALP) was elevated (266-284 U/L). Whole-exome sequencing revealed a hemizygous pathogenic nonsense mutation (c.500G > A, p.Trp167Ter) in the PHEX gene. Brain MRI showed a congenital hydrocephalus and Arnold-Chiari malformation, type I. Renal ultrasound revealed no dilation of the upper urinary tract, and eGFR was 157.7 mL/min, confirming preserved kidney function. Results The patient started burosumab therapy-1.3 mg/kg subcutaneously every 4 weeks. After starting burosumab, serum phosphate steadily rose from 0.61-0.70 mmol/L to 0.81 mmol/L, while ALP activity was trending downward. The serum calcium levels and the renal function have remain stable within the normal range. The patient reported an improvement in overall well-being and significant pain reduction. No adverse effects were noted. Discussion X-linked hypophosphatemic rickets (XLH) remains a diagnostic and therapeutic challenge due to its rarity and variable clinical presentation. Delayed recognition often leads to irreversible skeletal deformities and functional limitations. The introduction of burosumab has changed the treatment paradigm by directly targeting the underlying pathophysiology of phosphate wasting. This case contributes to the growing clinical experience demonstrating the importance of timely diagnosis and access to targeted therapies in improving long-term outcomes for patients with XLH. Conclusions Burosumab provides significant biochemical and clinical benefits in patients with severe phenotype of XLH in adults. Additional studies are needed to further study the effects of burosumab and optimal use in the management of adult XLH.