Poster Presentation ESA-SRB-APEG-NZSE 2022

Denosumab for Williams syndrome associated hypercalcaemia   (#459)

Annabelle Hobbs 1 , Erin Sharwood 1 2 , Rowena Lalji 2 3 4 5 , Craig Munns 1 2 6 7
  1. Department of Endocrinology, Queensland Children's Hospital, Brisbane, Queensland, Australia
  2. Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
  3. Department of Nephrology, Queensland Children's Hospital, Brisbane, Queensland, Australia
  4. Centre for Kidney Disease Research, University of Queensland, Brisbane, Queensland, Australia
  5. Metro South and Integrated Nephrology and Transplant Services (MINTS), Princess Alexandra Hospital, Brisbane, Queensland, Australia
  6. Child Health Research Centre, Brisbane, Queensland, Australia
  7. Mayne Academy of Paediatrics, Brisbane, Queensland, Australia

Aim

To describe denosumab use for hypercalcaemia associated with Williams syndrome (WS) and renal impairment.

Methods

Case report.

Results

A 20-month-old boy (AB) presented to his local hospital with a respiratory tract infection.  He had known WS, diagnosed after identification of severe supravalvular aortic stenosis aged 13 months.  

At presentation, AB had severe hypercalcaemia and renal impairment (Table)62fe0de37911a-Screen+Shot+2022-08-18+at+8.03.31+pm.png

The impression was that of chronic idiopathic hypercalcaemia, consistent with his diagnosis of WS.  AB was commenced on intravenous hyperhydration, mindful of impaired renal function.  Treatments trialled (Figure) included reduced calcium feeds, calcitonin, and prednisolone.  While there was improvement in serum calcium levels, none of these treatments achieved normocalcaemia. 

 62fe0c30b2dcb-Figure+1.png

AB’s hypercalcaemia rapidly improved following administration of 0.5mg/kg denosumab. This was repeated after 4 weeks due to rising serum calcium.  Eight weeks later his eGFR had improved to 40ml/min/1.73m1, however he subsequently experienced rebound hypercalcaemia. This was treated effectively with zoledronate given his improved renal function.

Mild to moderate idiopathic hypercalcaemia is well described in WS.2 Bisphosphonates have been successfully used to treat WS associated hypercalcaemia, however are not recommended with comorbid renal impairment due to risk of acute tubular necrosis3. 

Denosumab is a monoclonal antibody with affinity for nuclear factor-kappa ligand (RANKL), mimicking the inhibitory effect of OPG4.  It is used in hypercalcaemia management - primarily in adults with malignancy or hyperparathyroidism5,6. As denosumab is not renally cleared, it is considered safe in patients with renal impairment. There is a paucity of data in its use in paediatric hypercalcaemia, and its duration of action is unclear.  Concerns around rebound hypercalcaemia and bone and tooth development persist.

Conclusion

Denosumab is a novel treatment for paediatric hypercalcaemia when bisphosphonates are contraindicated.  It has not to our knowledge been previously described in WS.

 

 

 

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