Bone Abstracts

Background: Genetic disorders of mineral metabolism causing nephrolithiasis and bone abnormalities are uncommon and have a varied clinical spectrum. Hypophosphataemic rickets with hypercalciuria (HHRH) is a rare autosomal-recessive condition, typically presenting with severe rickets and hypophosphataemia. Milder forms can present with hypercalciuria and nephrolithiasis without bone disease. The underlying pathophysiology is due to mutations in the SLC34A3 gene, which encodes the sodium-phosphate transporter NaPi-IIc in the proximal renal tubules.

We describe HHRH in two siblings; the elder presented with hypercalciuria and nephrolithiasis, the younger subsequently diagnosed on biochemical screening; neither with clinical or radiological evidence of rickets or osteomalacia.

Presenting problem: A 13-year-old Caucasian girl from a non-consanguineous family presented with intermittent loin pain, macroscopic haematuria and passage of a kidney stone. Ultrasound showed a right-sided renal calculus and bilateral nephrocalcinosis. Recurrent episodes of calculi followed. Urine biochemistry demonstrated hypercalciuria (0.16 mmol/kg per day (normal <0.1)) and hyperphosphaturia (TmP/GFR 0.59 mmol/l (0.93–1.71)). Plasma analysis revealed hypophosphataemia 0.78 mmol/l (0.95–1.5), suppressed serum parathyroid hormone (9 pg/ml (15–65)), elevated serum 1,25-dihydroxyvitamin D 109 pg/ml (20–50) and inappropriately low FGF23 30 RU/ml considering the hypophosphataemia.

Clinical management: Genetic studies found a heterozygous missense mutation c.413C>T (a rare but known SNP) and a homozygous inframe deletion c.1576_1578delCTC. Parental DNA analysis found her mother 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. Screening of her 10-year-old brother revealed hypercalciuria (urine calcium:creatinine ratio 0.87 mol/mol), mild nephrocalcinosis on ultrasound, normal serum phosphate (1.25 mmol/l (1.0–1.8)), raised 1,25-dihydroxyvitamin D (252.0 pmol/l (48–120)) and FGF23 84 RU/ml. DNA analysis is awaited. Maternal biochemistry is also awaited.

Treatment of the index 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. Her brother will also be treated with oral phosphate.

Discussion: Only a few sporadic cases of HHRH without rickets are described worldwide. It is likely to be underdiagnosed and requires treatment with oral phosphate supplementation alone, without vitamin D supplementation, which will worsen the condition. Treatment with oral phosphate supplements may help to prevent renal calculi and worsening of renal function.