Abstract 149: Hyperphosphatemic familial tumoral calcinosis due to homozygous mutation at Leu366Arg: First case report

Abstract

Background: Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disabling autosomal recessive metabolic disorder characterized by hyperphosphatemia and manifestations ranging from progressive deposition of calcium phosphate crystals in the skin, soft tissues and bone, and hyperostosis. The most common cause of HFTC is related to loss-of-function mutations in GALNT3 (Polypeptide N-Acetylgalactosaminyl transferase 3) gene causing defective glycosylation of FGF23.Material and Methods: A 16 year boy presented with lump in the left gluteal area and hyperphosphatemia. Serum ionized calcium, alkaline phosphate, intact PTH, 25-OH vitamin D, serum creatinine and C terminal FGF 23, magnetic resonance imaging of hip, dental CBCT , bone mineral density at lumbar spine and hip by dual x-ray absorptiometry (DEXA) BMD, and 99Tc MDP bone scan, followed by next generation sequencing (NGS) and Sanger's sequencing.Results: A 16 year otherwise healthy boy presented with hard painless lump in the left gluteal area and hyperphosphatemia for last one year. His parents had third degree consanguinity with ancestral roots in Middle East. Father has small calcinosis in the right hand and mother was asymptomatic. Child had no associated bone pain, proximal muscle weakness, fracture or constitutional symptoms. S. phosphorus was 6.98mg/dl (normal: 3.5–5.5) with inappropriately increased TRP (95%) and TMP-GFR (7.2). Serum ionized calcium, alkaline phosphate, intact PTH, 25-OH vitamin D and serum creatinine were normal. MRI showed 5.7x3.7x3 cm lobulated heterogenous hypointensity near left greater trochanter. This mass was excised and showed tissue calcification. 99Tc-MDP bone scan and bone density parameters were normal. CBCT scan maxilla and mandible showed generalized hypercementosis with irregular root morphology. Serum C-terminal FGF 23 was 2401 RU/ml (normal: <150). NGS revealed normal FGF23 and Alpha Klotho genes. Exon 5 of GALNT3 gene showed homozygous mutation at Leu 366 Arg. GALNT3 Leu 366 Arg mutation causing HFTC has been described as compound heterozygous.Conclusion: This is the first case report of homozygous mutation at Leu366Arg causing HFTC.