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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.
- 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.
- 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.
- Renal tubular acidosis.
- Hereditary hypophosphataemic rickets with hypocalciuria.
- Fanconi's syndrome.
- Vitamin D-deficient rickets.
- 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.
- 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.
- Calcitriol reduces 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.
- 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.
- 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.
- X-linked hypophosphataemic rickets is frequently associated with short stature, even when treatment is provided for a long time.
- Apart from the short stature, the prognosis is usually good with a normal lifespan.
Further reading and references
Hypophosphatemic Rickets, X-linked Dominant, XLHR; Online Mendelian Inheritance in Man (OMIM)
Roth KS; Hypophosphatemic Rickets, eMedicine, Feb 2009
Saggese G, Baroncelli GI; Hypophosphataemic rickets. Horm Res. 200053 Suppl 3:57-60.