X-linked hypophosphatemia

Epidemiology

• bony abnormalities are less common in women

Pathology

• reduced proximal tubular resorption of phosphate
• increased fractional excretion of phosphate
• osteomalacia develops in adult life
• overgrowth of bones at sites of muscular tendon attachment may compress nerves or limit movement
• increased secretion of FGF-23

Genetics

• X-linked inheritance

Clinical manifestations

• patients may be asymptomatic
• short stature, rachitic bones
• recurrent striss fractures
• dental abscesses
• legs are particularly short & deformed
• bone age & dentition are retarded
• skull becomes deformed
  • maxillofacial region may be abnormal

Laboratory

• serum chemistries
  • serum phosphorus: hypophosphatemia
  • alkaline phosphatase in serum is elevated
  • serum parathyroid hormone (PTH) is normal or high
  • serum calcium is normal
• urine chemistries
  • urine calcium: Ca+2 excretion is normal or low
  • glycine in urine: mild glycinuria
  • glucose in urine: glycosuria may occur

Management

• phosphate (NutraPhos) 1-4 g/day in divided doses
• calcitriol or some other form of vitamin D
• burosumab improves renal tubular phosphate reabsorption, serum phosphorus levels, linear growth, & physical function & reduces pain & severity of rickets
• orthopedic management
  • delay corrective surgery until active growth phase is complete (exception is genu valgum {knock knee})

More general terms

• genetic disease of bone/skeletal system
• hypophosphatemia

Database

• OMIM: https://mirror.omim.org/entry/307800