Clinical Scenario:
A 14-month-old boy presents with delayed walking, genu varum and widened wrists. He has limited sunlight exposure and poor dietary intake. Investigations show low-normal calcium, low phosphate, markedly elevated ALP, elevated PTH and markedly low 25-OH vitamin D.
Which mechanism best explains the hypophosphatemia?
A. ↓ Intestinal phosphate absorption
B. ↑ Renal phosphate loss
C. ↑ Renal phosphate reabsorption
D. ↓ FGF23 secretion
E. ↓ 1α-hydroxylase activity
Correct answer & Explanation:
Answer: B. ↑ Renal phosphate loss
Explanation
This child has nutritional vitamin D deficiency rickets. Vitamin D deficiency reduces intestinal calcium absorption, leading to secondary hyperparathyroidism. Increased PTH promotes renal phosphate excretion, resulting in hypophosphatemia, which contributes to defective mineralization of growing bone. The typical biochemical pattern includes low/low-normal calcium, hypophosphatemia, markedly elevated ALP, elevated PTH and low 25-OH vitamin D.
- A. ↓ Intestinal phosphate absorption: May contribute to phosphate deficiency in vitamin D deficiency, but the prominent mechanism producing hypophosphatemia in established rickets is PTH-mediated renal phosphate loss.
- C. ↑ Renal phosphate reabsorption: Would increase serum phosphate and therefore is incorrect.
- D. ↓ FGF23 secretion: Reduced FGF23 would decrease renal phosphate excretion, producing phosphate retention rather than hypophosphatemia.
- E. ↓ 1α-hydroxylase activity: In vitamin D deficiency, secondary hyperparathyroidism generally stimulates, rather than suppresses, renal 1α-hydroxylase activity.
Reference
Kliegman RM, St Geme JW, Blum NJ, Shah SS, Tasker RC, Wilson KM, eds. Nelson Textbook of Pediatrics. 22nd ed. Elsevier. Chapter 69: Vitamin D Deficiency (Rickets) and Excess.
