Three years follow-up of pamidronate therapy in two brothers with osteoporosis-pseudoglioma syndrome (OPPG) carrying an LRP5 mutation.
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.
Barros
Elizabete Ribeiro
ER
Division of Endocrinology, Federal University of São Paulo, Brazil. bete-endo@pesquisa.epm.br
Dias da Silva
Magnus R
MR
Kunii
Ilda S
IS
Lazaretti-Castro
Marise
M
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
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