E-Poster Presentation ESA-SRB-ANZBMS 2021

X-linked Hypophosphataemic Rickets in Australian Children: Prevalence and Burden of Disease (#750)

Craig F Munns 1 2 , Anne Morris 1 3 , Guy Eslick 1 4 , Aris Siafarikas 5 , Andrew Biggin 1 6 , Myra Poon 1 , Jenny Harrington 7 , Diane Jensen 8 , Margaret Zacharin 9 , Christine Rodda 10 , Peter Simm 11
  1. The Children's Hospital at Westmead, Westmead, NSW, Australia
  2. Children’s Hospital Westmead Clinical School, University of Sydney , Sydney , NSW, Australia
  3. Children’s Hospital Westmead Clinical School, The Children's Hospital At Westmead, Westmead, NSW, Australia
  4. Children’s Hospital Westmead Clinical School, The Children's Hospital At Westmead, Westmead, NSW, Australia
  5. Endocrinology , Perth Children's Hospital, Perth, Western Australia, Australia
  6. Children’s Hospital Westmead Clinical School, The Children's Hospital At Westmead, Westmead, NSW, Australia
  7. Endocrinology and Diabetes, The Women and Children's Hospital, Adelaide, South Australia, Australia
  8. Endocrinology and Diabetes, Queensland Children's Hospital, Brisbane, QLD, Australia
  9. Endocrinology and Diabetes, The Royal Children's Hospital , Melbourne, Victoria, Australia
  10. Endocrinology, Sunshine Hospital, Melbourne, Victoria, Australia
  11. Endocrinology and Diabetes, The Royal Children's Hospital, Melbourne, Victoria, Australia

X-linked Hypophosphataemic Rickets in Australian Children: Prevalence and Burden of Disease

 

Aim

  1. Estimate the national prevalence of x-linked hypophosphataemic rickets (XLH) in Australia.
  2. Describe the prevalent cases in terms of:
  3. Demographics
  4. Family history of XLH
  5. Presenting and current biochemical, clinical features and complications
  6. Therapies used to treat XLH

Methods

Case definition, child <18 years with XLH: Rickets during childhood AND Pathogenic mutation in the PHEX gene OR iFGF23 levels above the limits of the local laboratory range OR Family history that supports X-linked inheritance.

The study was conducted with the Australian Paediatric Surveillance Unit (APSU). In June and July 2020, 1434 paediatricians were asked if they had seen a child with XLH. Paediatricians completed a case report form for each child into a  REDCap database or sent to APSU via email.

Results:

47 paediatricians reported 1 or more cases of XLH. After exclusion of duplicates (10) and errors (5) there were 74 confirmed cases. The minimum national prevalence was 1.31 per 100,000 children under 18 years (CI 1.02 – 1.64). Current medial age 11.0 years (1-18), medial age at diagnosis 2.0 years (0.1-17), 59% female and 67% family history of XLH. PHEX gene testing in 49 children (65%) of which 47 had a pathogenic mutation.  Males were more likely to have bone and joint pain, kyphosis, tooth abscess and cransiosynostosis (p<0.05).

33 (45%) were managed with phosphate and calcitriol and 41 (55%) with Burosumab, which was associated with a higher serum phosphate level. Complications of phosphate and calcitriol therapy included nephrocalcinosis (32%), hyperparathyroidism (18%) and renal failure (1%).

Conclusion:

Prevalence of XLH in Australia is similar to other reported studies. XLH is associated with a significant burden of disease and males appeared more severely affected. Diagnosis is often delayed. Burosumab normalised serum phosphate in clinical use.

  1. 1. Imel EA, White KE. Pharmacological management of X-linked hypophosphataemia. Br J Clin Pharmacol. 2018.
  2. 2. Imel EA, Biggin A, Schindeler A, Munns CF. FGF23, Hypophosphatemia, and Emerging Treatments. JBMR Plus, 2019. May 13;3(8):e10190.
  3. 3. Schindeler A, Biggin A, Munns CF. Clinical Evidence for the Benefits of Burosumab Therapy for X-Linked Hypophosphatemia (XLH) and Other Conditions in Adults and Children. Front Endocrinol. 2020 May 28; 11:338
  4. 4. Imel EA, Glorieux FH, Whyte MP, Munns CF, Ward LM, Nilsson O, Simmons JH, Padidela R, Namba N, Cheong HI, Pitukcheewanont P, Sochett E, Högler W, Muroya K, Tanaka H, Gottesman GS, Biggin A, Perwad F, Mao M, Chen CY, Skrinar A, San Martin J, Portale AA. Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet, 2019 Jun 15;393(10189):2416-2427.