Bone Abstracts

Background: X linked hypophosphataemic rickets is the commonest cause of renal phosphate wasting, however sporadic cases may warrant additional investigations to exclude less common causes, as exemplified by our case.

Presenting problem: A 3 year 7 month boy was referred for assessment and ongoing management of rickets and short stature (height less than 1^st %.) He originally presented with leg bowing and waddling gait from the age of 12 months. His parents were non-consanguineous and there were no other affected relatives. He had been treated with routine cholecalciferol supplementation without biochemical or clinical improvement. Subsequently he was also diagnosed with a moderate intellectual disability (FSIQ 60). Initial investigations showed normal serum calcium, 25 Vitamin D and PTH, with a low serum phosphate (1.06 mmol/l), raised alkaline phosphatase (524 u/l), and a decreased tubular reabsorption of phosphate (TRP) of 85%.

Clinical management: With a clinical picture suggestive of X linked hypophosphataemic rickets, he was commenced on calcitriol and phosphate with initial clinical improvement. Measurement of ionised calcium lead to the recognition that he also had a persistently marked metabolic acidosis with a pH of 7.16. Further investigations revealed a raised protein:creatinine ratio of 0.17 g/mmol (0–0.03) and a low molecular weight (LMW) proteinuria (urine β-2 microglobulin 27200 μg/l (0–300) without evidence of a generalised tubulopathy. Renal ultrasound also demonstrated early nephrocalcinosis.

Discussion: LMW proteinuria is pathognomonic of Dent’s Disease which is defined by the additional clinical features of hypercalciuria with one of the following nephrocalcinosis/nephrolithiasis, haematuria, chronic kidney disease or suggestive family history¹. Dent’s disease is a heterogeneous group of X linked recessive disorders of variable phenotype associated with proximal tubular dysfunction and is typically associated with inactivating mutations of CLCN5. Extra renal manifestations, including intellectual disability are seen in Dent-2 disease associated with OCR1 mutations. Whole exome sequencing is awaited. We recommend careful assessment of acid base status and renal tubular function in all children (particularly male) presenting with sporadic hypophosphataemic rickets, as early recognition of Dent’s disease is important to ensure appropriate treatment and genetic counselling.

Disclosure: The authors declared no competing interests.

Reference
1. Devuyst O and Thakker RV. Dent’s Disease. Orphanet Journal of Rare Diseases 2010; 5:28.