title: Three years follow-up of pamidronate therapy in two brothers with osteoporosis-pseudoglioma syndrome (OPPG) carrying an LRP5 mutation.
abstract: Osteoporosis-pseudoglioma (OPPG) is a rare syndrome characterized by severe osteoporosis and ocular defects caused by homozygotic inactivation mutations in the LRP5 gene. Bisphosphonate has been demonstrated to improve bone mineral density (BMD) in children with OPPG. We present here a 3 years follow-up of two brothers with OPPG carrying a novel mutation in the LRP5 gene, who were treated with intravenous pamidronate.
  
  
  METHODS
  We looked for a mutation in the LRP5 gene in two brothers (12 and 4 years old) with clinical features of OPPG (blindness, low BMD and fragility fractures) and in their consanguineous parents to confirm the diagnosis of OPPG. The patients were treated with bisphosphonate for 3 years. They received 1 mg/kg/day of pamidronate for 2 consecutive days, every 3 months during the first year, and every 4 months in subsequent years. Calcium, phosphorus, total alkaline phosphatase, parathyroid hormone, hepatic transaminases, creatinine and hemogram tests were performed before each infusion. Bone densitometry was performed at baseline and at the end of the follow-up.
  
  
  CONCLUSIONS
  The affected brothers carry a missense mutation in the third codon of exon 8 (AAT-->ATT) that led to the exchange of an asparagine for an isoleucine (N531I). Both parents were found to be heterozygous for this mutation. The intravenous pamidronate therapy was safe for up to 3 years of use. Moreover, increased BMD and decreased fracture rate were observed in our patients with OPPG.
authors.affiliation: Division of Endocrinology, Federal University of São Paulo, Brazil. bete-endo@pesquisa.epm.br
authors.forename: Elizabete Ribeiro
authors.initials: ER
authors.lastname: Barros
authors.forename: Magnus R
authors.initials: MR
authors.lastname: Dias da Silva
authors.forename: Ilda S
authors.initials: IS
authors.lastname: Kunii
authors.forename: Marise
authors.initials: M
authors.lastname: Lazaretti-Castro
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001766:Blindness / Q000150:complications* / Q000151:congenital / Q000235:genetics; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004164:Diphosphonates / Q000627:therapeutic use*; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000517:prevention & control; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008297:Male; D009154:Mutation; D010024:Osteoporosis / Q000150:complications* / Q000235:genetics; D000077268:Pamidronate; D010375:Pedigree; D035781:Siblings; D013577:Syndrome
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D000077268:Pamidronate