The pathophysiology of hypophosphatemia

Area of Science:

• Endocrinology
• Nephrology
• Genetics

Background:

• Fibroblast growth factor (FGF) 23 is identified as a key regulator of serum inorganic phosphate (Pi) levels.
• Disorders causing hypophosphatemic rickets/osteomalacia are now better understood.
• Measurement of intact FGF23 is a valuable diagnostic tool for chronic hypophosphatemia.

Purpose of the Study:

• To clarify the etiology of chronic hypophosphatemia.
• To categorize causes of hypophosphatemia into FGF23-related, primary tubular dysfunction, vitamin D metabolism disturbance, and PTH1R-mediated groups.
• To introduce a diagnostic flowchart for chronic hypophosphatemia.

Main Methods:

• Classification of chronic hypophosphatemia etiologies into four main groups.
• Subdivision of each group into inherited and acquired forms.
• Review of specific conditions like ectopic FGF23 syndrome and vitamin D-dependent rickets type 3.

Main Results:

• Chronic hypophosphatemia etiology is categorized into FGF23-related, primary tubular dysfunction, vitamin D metabolism disturbance, and PTH1R-mediated causes.
• Both inherited and acquired forms within each category are described.
• Specific examples illustrate the diverse causes.

Conclusions:

• Intact FGF23 measurement is crucial for diagnosing chronic hypophosphatemia.
• Bone-specific alkaline phosphatase (BAP) helps differentiate acute/subacute from chronic hypophosphatemia.
• A systematic approach, including a diagnostic flowchart, aids in managing hypophosphatemic disorders.