Bone Abstracts

: Hyperphosphatemic tumoral calcinosis (HTC) is a rare autosomal recessive metabolic disorder characterized by ectopic calcifications due to progressive deposition of basic calcium phosphate crystals in soft tissues. The biochemical hallmark of HTC is hyperphosphatemia caused by increased renal absorption of phosphate due to loss-of-function mutations in three genes: in the fibroblast growth factor-23 gene (FGF23) coding for a potent phosphaturic protein, in GALNT3, gene which encodes a glycosyltransferase responsible for FGF23 O-glycosylation or in KL encoding Klotho, which serves as a co-receptor for FGF23. Only one case of tumoral calcinosis due to a homozygous mutation in KL and FGFR1 were recently reported. We report the case of an 8-month-old infant who presented a large painful subcutaneous calcified lesion of the forearm with no history of trauma. His blood work showed elevated fasting serum phosphate levels (Ph: 2.6 mmol/l), inappropriately elevated tubular maximum phosphate reabsorption per unit glomerular filtration rate (TmP/GFR), associated with increased levels of intact FGF23 (5N). Renal function and ionized calcium level were normal with a normal PTH level. Because of progression of the lesion interfering with elbow movements, naproxen therapy was started. The naproxen appeared to be effective on pain and was well tolered. Elbow function improved in a few weeks. We observed a regression of the calcifications on the radiograph after 8 months of treatment. Six months after stopping the therapy, he is asymptomatic. However, FGF 23 levels remain high with slightly increased Phosphate and normal calcium levels. Persistently elevated FGF23 levels associated with hyperphosphatemia highly suggest a KL mutation. Nevertheless no mutation was found in KL, neither in FGF23 and GALNT3 analyzed by CGH analysis and direct sequencing. However, the first 99 amino acids of the KL gene could not be sequenced due to the high GC dinucleotide content. Exome sequencing might allow us to find a possible mutation of KL and this analysis is underway. In summary, we identified a patient with HTC suspected biochemically of having a Klotho mutation (would be only second patient to be reported), but more genetic investigations are required to localize the mutation.

Disclosure: The authors declared no competing interests.