Name two diseases causing hypophosphatemic rickets and their genetic basis.

Name two diseases causing hypophosphatemic rickets and their genetic basis.

• A. X-linked hypophosphatemic rickets (PHEX mutation) and autosomal dominant hypophosphatemic rickets (FGF23 or related mutations).
• B. X-linked hypophosphatemic rickets (PHEX mutation) and autosomal recessive hypophosphatemic rickets (DMP1 mutation).
• C. Hypophosphatemic rickets due to vitamin D deficiency.
• D. Autosomal dominant rickets due to vitamin D receptor mutation.

Answer: (D)

Hypophosphatemic rickets comes from the kidney wasting phosphate due to excess FGF23 signaling, which lowers renal phosphate reabsorption and reduces active vitamin D. The two well-established genetic forms are: - X-linked hypophosphatemic rickets caused by loss-of-function mutations in PHEX. PHEX normally helps regulate FGF23; when it’s defective, FGF23 levels rise, leading to phosphate wasting and rickets. - Autosomal dominant hypophosphatemic rickets caused by gain-of-function mutations in FGF23 (or related regulatory mutations) that increase FGF23 activity, again promoting phosphate loss in the kidneys and impaired bone mineralization. Vitamin D deficiency causes a different pattern of rickets (often with low calcium and different phosphate dynamics), and a vitamin D receptor mutation produces a distinct hereditary vitamin D–resistant picture, not the classic hypophosphatemic rickets caused by FGF23/PHEX dysregulation.

Hypophosphatemic rickets comes from the kidney wasting phosphate due to excess FGF23 signaling, which lowers renal phosphate reabsorption and reduces active vitamin D. The two well-established genetic forms are:

• X-linked hypophosphatemic rickets caused by loss-of-function mutations in PHEX. PHEX normally helps regulate FGF23; when it’s defective, FGF23 levels rise, leading to phosphate wasting and rickets.

• Autosomal dominant hypophosphatemic rickets caused by gain-of-function mutations in FGF23 (or related regulatory mutations) that increase FGF23 activity, again promoting phosphate loss in the kidneys and impaired bone mineralization.

Vitamin D deficiency causes a different pattern of rickets (often with low calcium and different phosphate dynamics), and a vitamin D receptor mutation produces a distinct hereditary vitamin D–resistant picture, not the classic hypophosphatemic rickets caused by FGF23/PHEX dysregulation.