ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2016) 45 OC3.1 | DOI: 10.1530/endoabs.45.OC3.1

A case of rare type of Rickets with unidentified genetic aetiology

Ved Bhushan Arya, Caroline Brain & Jeremy Allgrove

Great Ormond Street Hospital, London, UK.

A 3-years-old young girl, born to Caucasian non-consanguineous parents, presented with bowed legs, noticed since the age of 18-months. She had no significant past medical or family history. On examination, her height was −1.3 SDS (Mid parental height +1.87 SDS). She had widened wrists, genu varum and rachitic rosary. She had areas of skin hyperpigmentation on left forearm and anterior thigh.

Investigations showed low 25-OH Vitamin D (35 nmol/l), normal serum calcium (2.35 mmol/l), low serum phosphate (0.68 mmol/l), elevated alkaline phosphatase (570 u/l) and normal PTH (6.3 pmol/l). X-rays of wrists confirmed rickets. Treatment with a 3-months course of 3000 IU daily of cholecalciferol resulted in no biochemical and radiological improvement. Follow-up investigations showed normal 25-OH Vitamin D (146 nmol/l), normal serum calcium (2.46 mmol/l), persistently low serum phosphate (0.77 mmol/l) and elevated serum alkaline phosphate (657 u/l).

In view of low serum phosphate, tubular reabsorption of phosphate (TRP) was measured which was normal (81%; normal 70 – 100%). When TRP was corrected for low serum phosphate, it confirmed urinary phosphate wasting (TmP/GFR 0.56; normal range 1.10–2.70) and suggested a diagnosis of hypophosphataemic rickets. Elevated serum FGF23 levels (215 HRU/ml; Normal < 100), confirmed FGF23 mediated phosphaturia. Treatment with alphacalcidol (30 ng/kg) and oral phosphate (3 mmol/kg/d) resulted in gradual improvement in rickets.

No mutation was identified on sequencing of PHEX gene, excluding X-linked hypophosphataemic rickets, the commonest cause of hypophosphataemic rickets. Subsequently Sanger sequencing of FGF23, DMP1 and ENPP1 was performed, which did not identify any mutation either, excluding autosomal dominant and recessive hypophosphataemic rickets. Investigations (urine amino acids, urine glucose and tubular damage markers) for Fanconi syndrome were negative as well.

Although the skin lesions were not classical of McCune-Albright syndrome and there was no evidence of fibrous dysplasia or endocrinopathy, sequencing of GNAS1 from lymphocyte DNA and subsequently fibroblast DNA was undertaken, which was normal. Punch biopsy of the skin lesions was performed, which ruled out the diagnosis of epidermal naevi (known to be associated with hypophosphataemic rickets). Unfortunately FGF23 staining of sections of skin lesions is not available to establish these skin lesions to be the source of FGF23 and cause of hypophosphataemic rickets.

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