Bone Abstracts

Background: Hypophosphataemic rickets (HPR) is an inherited condition of phosphate wasting associated with abnormal bone biochemistry and features of rickets. Most patients respond to treatment with alfacalcidol and oral phosphate. Raised levels of alkaline phosphatase (ALP) and parathyroid hormone (PTH) generally indicate a need for refining treatment, or poor compliance.

Presenting problem: We report the case of a 36 week gestation male infant born to consanguineous South Asian parents, in whom HPR is resistant to conventional treatment. He required ventilation for bilateral choanal stenosis at 3 days of age and had craniofacial abnormalities. Direct sequencing of the FAM20C gene revealed a homozygous missense mutation in exon 6, confirming Raine syndrome. Features of this rare condition include osteosclerosis, craniofacial anomalies, choanal atresia and thoracic hypoplasia. Appositional new bone formation may resemble prenatal and postnatal fractures but HPR has not been previously described.

Metabolic bone disease: At two months, he had elevated ALP (5605 iu/l, reference range 187–1197), hypophosphataemia (0.75 mmol/l, (1.36–2.26)) and hypocalcaemia (1.92 mmol/l, (2.20–2.79)). Serum PTH was elevated (72 pmol/l, (1.1–6.9)) and vitamin D levels were suboptimal (<40 nmol/l). Wrist radiographs showed features in keeping with vitamin D deficiency rickets.

Clinical management: Treatment with vitamin D and calcium failed to normalize biochemistry. Analysis of urine revealed low tubular reabsorption of phosphate (72%) despite hypophosphataemia. FGF23 was raised (157 RU/ml, (0–100)), with normal 1,25 dihydroxy vitamin D, suggesting an FGF23 dependent condition akin to hereditary HPR. Treatment with increasing doses of alfacalcidol and phosphate have marginally improved bone chemistry, but PTH and ALP remain elevated at 3 years, despite normal phosphate and vitamin D levels. Radiological signs of rickets have persisted and he has recently developed nephrocalcinosis.

Discussion: Of the 24 known cases of Raine Syndrome to date, only one has been reported to have hypophosphataemia with elevated ALP.

FAM20C is known to code for the human homologue of dentin matrix protein 4 (DMP4), which is expressed in bone. It may be similar to dentin matrix protein 1 which has a role in inherited forms of hypophosphataemic rickets. Our patient has biochemical features of hypophosphataemic rickets, which has to date been resistant to conventional treatment.

Disclosure: The authors declared no competing interests.