Hypophosphataemic Rickets

Hypophosphataemic rickets is characterised by growth retardation, rickets or osteomalacia, hypophosphataemia, and renal defects in phosphate reabsorption and in vitamin D metabolism. 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.

• Rare.
• The degree of bone involvement is much less severe in heterozygous females.

• Slow growth rate in the first year of life.
• Reluctance to weight-bear when beginning to stand or walk.
• Maternal family history is likely to include short stature and rickets.
• Older children may have late dentition or 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.

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

• Urinary loss of phosphate is increased because of decreased renal tubular reabsorption of phosphate.
• Hypophosphataemia.
• Serum calcium levels may be normal or slightly low, alkaline phosphatase levels are significantly increased, serum parathyroid hormone level is normal or slightly elevated, and calcitriol level is low or normal.
• 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.

• 1, 25-dihydroxyvitamin D(3) or 1alpha-hydroxyvitamin D(3) plus inorganic phosphate salts.
• In some poorly growing patients, long-term growth hormone therapy given with conventional treatment improves linear growth.¹
• Calcitriol substantially diminishes but does not eliminate the risk of hypercalcaemic episodes, which may be frequent with vitamin D treatment.
• Amiloride and hydrochlorothiazide are given to increase calcium reabsorption and reduce the risk of nephrocalcinosis.
• 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.

• 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 has been reported, caused by persistent hyperparathyroidism.

• X-Linked hypophosphataemic rickets is frequently associated with short stature, even when treatment is provided for a long time.¹
• Apart from the short stature of most affected adults, the prognosis is good, with a normal lifespan and normal health.