title: Familial tumoral calcinosis caused by a novel FGF23 mutation: response to induction of tubular renal acidosis with acetazolamide and the non-calcium phosphate binder sevelamer.
abstract: Hyperphosphatemic familial tumoral calcinosis (HFTC) is an uncommon disease characterized by periarticular calcifications produced by the deposition of amorphous extraosseous calcifications of hydroxyapatite. It is associated with hyperphosphatemia due to increased tubular phosphate reabsorption, despite normal renal function and normal plasma PTH levels. The disease can be caused by inactivating mutations in either the fibroblast growth factor 23 (FGF23) gene, the UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) gene or in human KLOTHO (KL) gene. Herein, we describe a Caucasian 3-year-old girl with tumoral calcinosis who presented with elevated serum phosphorus levels and a large calcified mass at her left elbow which led to ulceration of the skin. Treatment with the phosphate binder sevelamer and the carbonic anhydrase inhibitor acetazolamide successfully reduced the serum phosphate levels and led to a reduction of the calcified mass. This medical management has not been described previously. Her 7-month-old sister also had elevated serum phosphate levels, but did not have ectopic calcifications. Sequencing analysis revealed a novel homozygous FGF23 missense mutation (c.367G>T, p.Gly123Trp) in both siblings while the parents were carriers of the mutation.
authors.affiliation: Institute of Maternal and Child Research, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Juan Javier
authors.initials: JJ
authors.lastname: Lammoglia
authors.forename: Veronica
authors.initials: V
authors.lastname: Mericq
mesh_terms: D000086:Acetazolamide / Q000009:adverse effects / Q000627:therapeutic use*; D000141:Acidosis, Renal Tubular / Q000139:chemically induced* / Q000235:genetics; D002114:Calcinosis / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D002614:Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics*; D006801:Humans; D054559:Hyperphosphatemia / Q000150:complications / Q000235:genetics; D007223:Infant; D009154:Mutation / Q000502:physiology; D009369:Neoplasms / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D010710:Phosphates / Q000378:metabolism; D011073:Polyamines / Q000009:adverse effects / Q000627:therapeutic use*; D000069603:Sevelamer; D035781:Siblings; D016896:Treatment Outcome
chemical_list: D002614:Chelating Agents; D004232:Diuretics; C000717427:FGF23 protein, human; D010710:Phosphates; D011073:Polyamines; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000069603:Sevelamer; D000086:Acetazolamide