Makindo Medical Notes

Related Subjects: |Vitamin D Replacement |Osteomalacia-Rickets-Vitamin D |Vitamin D resistant rickets |Vitamin D (25 OH D) Testing |X linked Hypophosphataemic rickets |Osteoporosis

In Hypophosphatemic Rickets, there is renal phosphate wasting and hypophosphatemia. Patients typically do not respond to standard Vitamin D therapy.

About

• Hypophosphatemic Rickets: Also known as Vitamin D-Resistant Rickets, a condition characterized by defective renal phosphate reabsorption leading to bone weakening and growth abnormalities.
• X-linked dominant inheritance pattern, though autosomal recessive and sporadic forms also exist.
• It is most commonly diagnosed in children with rickets that fail to respond to standard Vitamin D therapy.

Renal Tubular (RT) Forms

• Type I: Characterized by low renal 1-alpha-hydroxylase activity, resulting in insufficient activation of Vitamin D.
• Type II: Defined by end-organ resistance to 1,25-dihydroxyvitamin D₃ (the active form of Vitamin D).
• Both forms are treated with large doses of calcitriol (1,25-dihydroxy-vitamin D).

Aetiology

• Decreased proximal renal tubular reabsorption of phosphate, leading to excessive phosphate loss in urine (phosphate wasting).
• This results in hypophosphatemia, which impairs bone mineralization and leads to rickets.
• Decreased intestinal absorption of calcium and phosphate due to defective activation of Vitamin D.

Clinical Features

• Usually diagnosed in infants or young children with signs of rickets.
• Short stature: Growth failure and bone deformities, particularly affecting the femur and tibia (bowed legs).
• Delayed dentition: Abnormally delayed or incomplete development of teeth, often associated with dental abscesses.
• May present with other features such as:
  • Deafness
  • Chiari malformation: Structural defects in the cerebellum.
  • Calcification of soft tissues: Including tendons, ligaments, and joint capsules.
  • Craniosynostosis: Premature fusion of skull bones.
  • Renal stones: Due to abnormal calcium metabolism.

Investigations

• ↓ Serum phosphate (PO₄) levels.
• ↑ Alkaline phosphatase (ALP) due to increased bone turnover.
• ↑ Urinary phosphate excretion, reflecting renal phosphate wasting.
• ↓ Serum calcium (in some cases).
• ↑ Parathyroid hormone (PTH) due to secondary hyperparathyroidism.
• Normal 25-hydroxyvitamin D levels (but the active form is deficient).
• Renal ultrasound (USS) may reveal kidney stones or nephrocalcinosis.

Management

• Large doses of 1,25-dihydroxy-vitamin D (calcitriol) to compensate for defective Vitamin D metabolism.
• Oral phosphate supplements to replace the phosphate lost in urine.
• Growth hormone therapy may be considered to promote growth in affected children.
• Amiloride or thiazide diuretics may be used to enhance calcium reabsorption, reducing the risk of nephrocalcinosis (calcium deposition in the kidneys).

References

• Vitamin D Resistant Rickets