What is the most likely cause of an 18-month-old infant's delayed walking, widened lower ends of long bones, hypophosphatemia, and elevated alkaline phosphatase levels?

Vitamin D Deficient Rickets

The most likely diagnosis is Vitamin D deficient rickets (Option C), given the combination of delayed walking at 18 months, widened metaphyses of long bones, low-normal calcium (8.1 mmol/L), normal phosphate (2.1 mmol/L), and markedly elevated alkaline phosphatase (1020 U/L). 1, 2

Diagnostic Reasoning

Why Vitamin D Deficient Rickets is Most Likely

• The phosphate level is normal (2.1 mmol/L, reference 1.3-2.3), which is the critical distinguishing feature that rules out phosphate-wasting disorders 1, 2
• The calcium is low-normal (8.1 mmol/L), consistent with vitamin D deficiency where calcium absorption from the gut is impaired 3
• Markedly elevated alkaline phosphatase (1020 U/L, normal 100-320) indicates active rickets, as bone-specific ALP represents 80-90% of total ALP in children and is a reliable biomarker for rickets activity 2
• Clinical presentation at 18 months with delayed walking and widened metaphyses is classic for nutritional rickets, which typically manifests during the second year of life when weight-bearing begins 1

Why Other Options Are Excluded

Hypophosphatasia (Option A) is ruled out because:

• Hypophosphatasia presents with low or low-normal alkaline phosphatase, not elevated 4, 5, 6
• This patient has ALP of 1020 U/L, which is 3-fold elevated, the opposite of what occurs in hypophosphatasia 4

Familial hypophosphatemic rickets/XLH (Option F) is ruled out because:

• XLH presents with hypophosphatemia (low phosphate) due to renal phosphate wasting 1, 2
• This patient has normal phosphate levels (2.1 mmol/L) 1
• The American College of Nephrology states that low phosphate with elevated ALP suggests rickets or XLH, but normal phosphate excludes phosphate-wasting disorders 2

Renal osteodystrophy (Option B) is unlikely because:

• Renal osteodystrophy typically presents with both hypocalcemia and hyperphosphatemia due to impaired renal function 1
• This patient has normal phosphate, making significant renal impairment unlikely 1
• No mention of acidosis, glucosuria, or other features of renal tubular disease 1

Clinical Context and Pitfalls

Key Diagnostic Pearls

• Always check phosphate levels when evaluating rickets - this single value distinguishes vitamin D deficiency (normal/high phosphate) from hereditary hypophosphatemic rickets (low phosphate) 1, 2
• Do not use adult reference ranges - age-specific pediatric ranges are essential for interpreting ALP in toddlers 2
• Elevated bone-specific ALP is the most reliable biomarker for active rickets and helps assess disease severity 2

Common Pitfalls to Avoid

• Do not assume all elevated ALP in toddlers is physiologic - while ALP is physiologically higher in children due to skeletal growth, a 3-fold elevation (1020 vs 320 U/L upper limit) is pathologic 2
• Nutritional rickets and XLH can coexist - if phosphate levels do not normalize after vitamin D supplementation, consider XLH as an additional diagnosis 1
• In infants with congenital rickets, maternal vitamin D deficiency is the cause in 96% of cases (24/25), with maternal 25-hydroxyvitamin D levels typically <10 ng/mL 3