Case Report: A case of x-linked hypophosphatemic rickets complicated with polyostotic fibrous dysplasia caused by PHEX gene mutation and literature review.

We report a rare case of a 60-year-old male patient with X-linked hypophosphatemic rickets (XLH) caused by a PHEX gene mutation complicated with polyostotic fibrous dysplasia (FD). The patient presented with bilateral lower limb deformity for 59 years and recurrent fractures for 30 years. Physical examination revealed short stature (113 cm), multiple skeletal deformities, and limited joint mobility. Laboratory investigations showed persistent hypophosphatemia (0.43 mmol/L), elevated alkaline phosphatase (262 U/L), and increased urinary phosphorus excretion. Imaging studies demonstrated both typical features of XLH, including brush-like changes at the metaphysis of long bones and bowing deformity of the lower limbs, as well as characteristic findings of FD such as "ground-glass" appearance in the skull and femur. Genetic analysis identified a missense mutation NM_000444.6:c.1946G>T (p.Gly649Val) in the PHEX gene, which was classified as "Likely Pathogenic" according to ACMG guidelines. The patient was treated with oral phosphate preparations combined with calcitriol, resulting in gradual normalization of serum phosphorus levels and significant relief of bone pain symptoms.​ To our knowledge, this represents the first reported case of PHEX gene mutation-associated XLH combined with polyostotic FD. This case enriches the clinical phenotype spectrum of rare bone disorders and highlights the importance of comprehensive evaluation for patients presenting with hypophosphatemia and complex skeletal abnormalities. Clinicians should consider the possibility of concurrent hereditary phosphate metabolic disorders and bone dysplasias, and integrate clinical manifestations, imaging findings, and multi-gene testing for accurate diagnosis and individualized management. Further studies are needed to elucidate the underlying mechanism of this unique combination of two distinct genetic bone disorders.

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