X-Linked Hypophosphatemia with Whole Aspects

X-linked hypophosphatemia (XLH) is a rare genetic disorder caused by mutations in the PHEX gene,
and it is a primary example of a genetic cause of hypophosphatemia. The key effect of the PHEX muta-
tion is the overproduction of fibroblast growth factor 23 (FGF23), a known phosphatonin. Elevated
FGF23 levels lead to renal phosphate wasting, reduced synthesis of 1,25(OH)2D, and decreased para-
thyroid hormone levels. Chronic elevation of FGF23 is the root cause of lifelong hypophosphatemia.
This ongoing phosphate deficiency leads to impaired growth, poor bone mineralization, and a variety
of skeletal, dental, auditory, and cardiovascular issues, all of which negatively impact quality of life
and may contribute to premature mortality. While phosphate supplementation and 1,25(OH)2D ther-
apy remain foundational treatments, strategies targeting FGF23 have shown promising results and
gained greater importance over the last decade. X-linked hypophosphatemia is a complex, multisys-
tem condition with lifelong effects, requiring a multidisciplinary approach to care.