A gene (PEX) with homologies to endopeptidases is mutated in patients with X–linked hypophosphatemic rickets
A 71-year-old woman presented at the outpatient clinic for the first time in 1973 with diffuse bone pain mainly in both wrists, shoulders and the spine. Clinical examination showed limb deformities (genu varum of the left leg, genu valgum of the right leg) and short stature (142 cm). At that time, she had already experienced multiple spontaneous fractures of the right and left femur. There was no family history of bone disorders (mother and father as well as seven brothers and sisters were healthy). Laboratory tests at that moment showed: sodium 141 mmol/L (normal range 133–145), potassium 3.9 mmol/L (3.5–5.1), chloride 104 mmol/L (95–108), bicarbonate 23 mmol/L (23–29), calcium 9.8 mg/dL (8.4– 10.2), phosphate 1.7 mg/dL (2.4–4.5), serum creatinine 0.72 mg/dL and alkaline phosphatase 120 U/L (53– 141). Hyperparathyroidism was excluded. Urine analysis showed a daily phosphate excretion of 597 mg (300– 1300), a daily calcium excretion of 39 mg (100–250) and a daily creatinine excretion of 852 mg (660–2200), corresponding to a fractional renal excretion of phosphate of 67%. At that time, the diagnosis of a congenital disorder with hypophosphataemia due to renal phosphate wasting, resulting in osteomalacia was considered. Treatment with oral phosphate and vitamin D replacement was initiated, resulting in a normalization of her serum calcium and phosphate. The following years, a few episodes of symptomatic hypoand hypercalcaemia (with nausea and vomiting) could not be prevented. Figure 1 shows the evolution over the years of the serum calcium and phosphate levels. Figure 2 shows the evolution of the daily urinary excretion of calcium and phosphate.