title: Association between compound heterozygous mutations of SLC34A3 and hypercalciuria.
abstract: BACKGROUND
  Mutations in SLC34A3 have been shown to cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Patients with compound heterozygous or homozygous mutations develop skeletal lesions in addition to hypercalciuria, hypophosphatemia and/or elevated 1,25-dihydroxy vitamin D [1,25-(OH)2D] levels. Here, we report a case of hypercalciuria without skeletal lesions in a patient with compound heterozygous mutations of SLC34A3.
  
  
  METHODS
  A 3-year-old girl presented with microscopic hematuria. Laboratory data revealed elevated 1,25-(OH)2D levels and serum calcium, reduced serum inorganic phosphorus and hypercalciuria. In addition, the ratio of maximal rate of renal tubular reabsorption of phosphate to glomerular filtration rate was reduced. Abdominal ultrasound revealed bilateral nephrocalcinosis. These data were consistent with HHRH, but the patient had no clinical features of rickets or any family history of skeletal disease. Genetic analysis revealed compound heterozygous mutations of c.175+1 G>A and c.1234 C>T in SLC34A3.
  
  
  CONCLUSIONS
  This is the report of a patient with compound heterozygous mutations of SLC34A3 and normal skeletal features. Biallelic mutations in SLC34A3 can thus be associated with hypercalciuria not accompanied by rickets. Orally administered inorganic phosphate is predicted to improve symptoms in these patients, hence screening for SLC34A3 mutations should be considered in patients with hypercalciuria of unknown etiology.
authors.affiliation: Department of Pediatrics, Niigata City General Hospital, Niigata, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Abe
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nagasaki
authors.forename: Toru
authors.initials: T
authors.lastname: Watanabe
authors.forename: Tokinari
authors.initials: T
authors.lastname: Abe
authors.forename: Maki
authors.initials: M
authors.lastname: Fukami
mesh_terms: D000284:Administration, Oral; D002675:Child, Preschool; D053098:Familial Hypophosphatemic Rickets / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D053565:Hypercalciuria / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D009397:Nephrocalcinosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics; D010710:Phosphates / Q000008:administration & dosage; D050615:Sodium-Phosphate Cotransporter Proteins, Type IIc / Q000235:genetics*; D014463:Ultrasonography
chemical_list: D010710:Phosphates; C493562:SLC34A3 protein, human; D050615:Sodium-Phosphate Cotransporter Proteins, Type IIc