Endocrine Abstracts

Hypophosphataemic rickets with hypercalciuria (HHRH) is a rare autosomal-recessive condition, typically reported in consanguineous families. Milder forms, with less significant hypophosphataemia, present with hypercalciuria and nephrolithiasis, without bone disease and may be underdiagnosed. The underlying pathophysiology is due to mutations in the SLC34A3 gene, which encodes a sodium-phosphate transporter in the proximal renal tubules. Our patient, a 13-year-old Caucasian girl from a non-consanguineous family, presented with a history of intermittent loin pain, haematuria and passage of a kidney stone. Ultrasound showed a right-sided renal calculus with bilateral nephrocalcinosis. She did not have clinical features of osteomalacia. Urine biochemistry showed hypercalciuria (0.2 mmol/kg per day (normal <0.1)) and hyperphosphaturia (TmP/GFR 0.59 mmol/l (0.93–1.71)), with hypophosphataemia 0.78 mmol/l (0.95–1.5), suppressed serum parathyroid hormone (9 pg/ml (15–65)) and elevated serum 1,25-dihydroxyvitamin D 109 pg/ml (20–50). Genetic studies found a heterozygous missense mutation c.413C>T (an extremely rare but known SNP) and a homozygous inframe deletion c.1576_1578delCTC. Parental DNA analysis found mother is heterozygous for both the missense mutation c.413C>T and the inframe deletion c.1576_1578delCTC, but no evidence of any mutation in her father. Treatment of the patient with oral phosphate supplements (introduced in incremental doses to prevent side-effects) has reduced urinary calcium excretion to 0.096 mmol/kg per day, with no further episodes of renal calculi. HHRH has only been described in a large Bedouin kindred and a few other sporadic cases worldwide. It is underdiagnosed and requires treatment with oral phosphate supplementation alone, without Vitamin D supplementation, which will worsen the condition. Treatment prevents renal calculi and allows normal bone development and growth.