X-linked Hypophosphatemic Rickets Revealed by Exome Sequencing: A Pediatric Case Report of a PHEX Pathogenic Variant.

X-linked hypophosphatemic rickets (XLH) is the most common form of hereditary vitamin-resistant rickets, caused by inactivating mutations of the PHEX (phosphate-regulating endopeptidase homolog, X-linked) gene, leading to elevated fibroblast growth factor 23 (FGF23) and chronic hypophosphatemia secondary to renal phosphate wasting. We report the case of a 3.5-year-old boy presenting with bilateral varus deformity of the lower limbs, frontal bossing, rachitic rosary, and growth retardation (-2.5 SD). Laboratory investigations revealed hypophosphatemia (0.88 mmol/L) with severely reduced urinary phosphate excretion (196.8 mg/24 h), elevated alkaline phosphatase (521 IU/L), and normal serum calcium and vitamin D levels. Exome sequencing identified a hemizygous pathogenic variant in PHEX: c.2192T>G (p.Phe731Cys), confirming the diagnosis of XLH. This case illustrates the decisive contribution of exome sequencing in confirming vitamin-resistant rickets and the importance of early diagnosis to prevent irreversible orthopedic sequelae.