Poster Presentation ESA-SRB-APEG-NZSE 2022

Extra-articular calcification in an adolescent boy: where history is paramount (#470)

Farrah Rodrigues 1 2 , Margaret Zacharin 1 2 3
  1. Paediatric Endocrinology and Diabetes, Royal Children's Hospital, Melbourne, Victoria, Australia
  2. Paediatrics, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
  3. Paediatrics, University of Melbourne, Melbourne, Victoria, Australia

A 15-year-old active boy, presented to a surgeon with a painful left elbow. There was no history of preceding trauma, he had full range of motion and was systemically well. Imaging demonstrated extra articular calcification at the distal humerus. Serum phosphate was elevated 2.53 mmol/L [1.10-1.80] with calcium 2.48 mmol/L [2.10-2.60] and tubular reabsorption of phosphate (TRP) of 94.6% [82-100%]. Endocrine assessment revealed a history of short tooth roots. A diagnosis of hyperphosphatemia due to a mutation in GALNT3 was suspected. Additional investigations revealed calcification of the left hip and nephrocalcinosis on renal ultrasound.  Dietary phosphate restriction and phosphate binder (Sevalmer) was commenced.

Over the following months, enlargement of the elbow lesion occurred, with worsening pain, reduced mobility limiting sporting activity, accompanied by deterioration of mental health. Serum phosphate remained elevated 2.22 mmol/L, calcium in normal range 2.31 nmol/L, low FGF23 13.6 ng/L [23.2 – 95.4 ng/L] with TRP of 98.04% [82-100%]. Imaging confirmed significant increase in calcification at both sites. Surgical resection was undertaken, due to marked joint restriction. Other medical interventions being trialled included acetazolamide (carbonic anhydrase inhibitor), IL1 blockade (Anakinra), monoclonal antibody against IL-1β and sodium thiosulfate.

Hyperphosphatemia Familial Tumoral Calcinosis is a rare, disabling disorder characterised by ectopic calcifications, painful swellings and enamel hypoplasia with bulbous tooth roots (1, 2).  Periarticular calcification leads to pain and reduced range of movement (1). It is caused by autosomal recessive inheritance of a pathological variant in either the gene encoding FGF23, GALNT3 or KLOTHO (1-3); resultant deficiency of/or resistance to the phosphate regulating hormone fibroblast growth factor 23(1, 3).  

The case underlines the importance of careful history, the unusual history of short tooth roots enabled rapid diagnosis. The aim of treatment is to reduce serum and urinary phosphate and to reduce pain; there is no definitive cure (1, 4).

  1. 1. Boyce AM, Lee AE, Roszko KL, Gafni RI. Hyperphosphatemic Tumoral Calcinosis: Pathogenesis, Clinical Presentation, and Challenges in Management. Frontiers in Endocrinology. 2020;11.
  2. 2. Rafaelsen S, Johansson S, Ræder H, Bjerknes R. Long-term clinical outcome and phenotypic variability in hyperphosphatemic familial tumoral calcinosis and hyperphosphatemic hyperostosis syndrome caused by a novel GALNT3 mutation; case report and review of the literature. BMC Genet. 2014;15:98.
  3. 3. Ito N, Fukumoto S. Congenital Hyperphosphatemic Conditions Caused by the Deficient Activity of FGF23. Calcif Tissue Int. 2021;108(1):104-15.
  4. 4.Freedman JD, Novak R, Bratman Morag S, Avitan-Hersh E, Nikomarov D. Bone Involvement in Hyperphosphatemic Familial Tumoral Calcinosis: A New Phenotypic Presentation. Rambam Maimonides Med J. 2021;12(3).