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Vol. 77, No. 2, 2012
Issue release date: April 2012
Horm Res Paediatr 2012;77:115–120

Osteoporosis-Pseudoglioma Syndrome: Three Novel Mutations in the LRP5 Gene and Response to Bisphosphonate Treatment

Tüysüz B. · Bursalı A. · Alp Z. · Suyugül N. · Laine C.M. · Mäkitie O.
Departments of aPediatric Genetics and bOphthalmology, Cerrahpaşa Medical School, Istanbul University, and cBaltalimanı Metin Sabanci Bone Diseases Education and Research Hospital, Istanbul, Turkey; dFolkhälsan Institute of Genetics, Biomedicum Helsinki, and ePediatric Endocrinology and Metabolic Bone Diseases, Children’s Hospital, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland

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Background/Aims: Osteoporosis-pseudoglioma (OPPG) syndrome is a rare disorder characterized by congenital or infancy-onset visual loss and severe juvenile osteoporosis. OPPG is caused by homozygous mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. We present three novel homozygous LRP5 mutations found in 3 unrelated Turkish children with consanguineous parents, along with clinical phenotypes and response to treatment with bisphosphonates (bisP). Methods/Results: The LRP5 gene was analyzed by direct sequencing after PCR amplification. Mutation screening for LRP5 revealed homozygous nonsense R1002X mutation in the first patient and homozygous missense mutations V336M and G507S in the second and third patient, respectively. The parents were heterozygous for these mutations. The patients’ eye symptoms began during the first months of life but the OPPG diagnoses were made based on skeletal deformities and osteopenia after 4 years of age. The patients’ bone mineral density Z scores were very low and consistent with osteopenia. All patients were treated with bisP for 3.5–7 years. Conclusion: We report three novel LRP5 mutations in 3 Turkish patients with OPPG. We show that the response of bisP therapy has improved the lumbar spinal bone mineral density Z scores and the patients’ quality of life as the bone pains decreased.

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