Hypophosphataemic Rickets

Hypophosphataemic rickets is characterised by growth retardation, rickets or osteomalacia, hypophosphataemia, and renal defects in phosphate reabsorption and in vitamin D metabolism.^[1] The X-linked form (X-linked dominant) is the most common with a defect in phosphate transport in the proximal tubule leading to persistent hypophosphataemia and high levels of phosphate in the urine. Much rarer autosomal dominant, recessive, and sporadic forms also occur.

Epidemiology

• Rare.
• The degree of bone involvement is much less severe in heterozygous females. However, there is often a maternal as well as paternal family history of short stature.^[2]

Presentation^[2]

• Slow growth rate in the first year of life.
• Reluctance to weight-bear when beginning to stand or walk.
• Late dentition, multiple dental abscesses.
• Intellectual development is unaffected.
• Widened joint spaces and flaring at the knees may become apparent in children by their first birthday, particularly in boys.
• When a child begins to stand and walk, bowing of the weight-bearing long bones develops quickly.

Differential diagnosis

• Cystinosis.
• Tyrosinaemia.
• Renal tubular acidosis.
• Hereditary hypophosphataemic rickets with hypocalciuria.
• Fanconi's syndrome.
• Vitamin D-deficient rickets.
• Pseudohypoparathyroidism.

Investigations

• Urinary loss of phosphate is increased because of decreased renal tubular reabsorption of phosphate.
• Blood tests for serum calcium, phosphate, alkaline phosphatase and parathyroid hormone:
  • Serum calcium levels may be normal or slightly low.
  • Phosphate levels are low.
  • Alkaline phosphatase levels are increased.
  • Parathyroid hormone level is normal or slightly raised.
• X-rays of the wrists, knees, ankles, and long bones: no pathognomonic signs distinguish hypophosphataemic rickets from any other aetiology.
• Periodic renal ultrasound is important to monitor for development of nephrocalcinosis.
• Monitoring the ratio of calcium to creatinine in the urine is also important (a urinary ratio of calcium to creatinine more than 0.25:1 requires reduction of the vitamin D dosage to avoid nephrocalcinosis).
• Patients under treatment should be carefully monitored for evidence of hyperparathyroidism.

Management

• Calcitriol (1,25-dihydroxycholecalciferol) - standard vitamin D preparations are not effective.
• In some poorly growing patients, long-term growth hormone therapy given with conventional treatment improves linear growth.^[3]
• Calcitriol reduces but does not eliminate the risk of hypercalcaemic episodes, which may be frequent with vitamin D treatment.^[2]
• Amiloride and hydrochlorothiazide are given to increase calcium reabsorption and reduce the risk of nephrocalcinosis.^[2]
• Phosphate replacement is required because of the large urinary phosphate loss.
• Osteotomy may be necessary for children whose diagnosis was delayed or whose initial treatment was inadequate.
• Skull deformity may require treatment for synostosis.
• Dental abscesses often require dental treatment.

Complications

• Short stature, which is disproportionate, resulting from deformity and growth retardation of lower extremities.
• Acute hypercalcaemia may occur during treatment.
• Nephrocalcinosis, which does not usually progress to renal failure.
• Hypertension may occur as a result of persistent hyperparathyroidism.

Prognosis

• X-linked hypophosphataemic rickets is frequently associated with short stature, even when treatment is provided for a long time.^[3]
• Apart from the short stature, the prognosis is usually good with a normal lifespan.