Osteoporosis-pseudoglioma syndrome in four new patients: identification of two novel LRP5 variants and insights on patients' management using bisphosphonates therapy.

Autor: Abdel-Hamid MS; Medical Molecular Genetics Department, Institute of Human Genetics and Genome Research, National Research Centre, Tahrir street, Dokki, Cairo, Egypt. mohamadnrc@hotmail.com., Elhossini RM; Clinical Genetics Department, Institute of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt., Otaify GA; Clinical Genetics Department, Institute of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt., Abdel-Ghafar SF; Medical Molecular Genetics Department, Institute of Human Genetics and Genome Research, National Research Centre, Tahrir street, Dokki, Cairo, Egypt., Aglan MS; Clinical Genetics Department, Institute of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA [Osteoporos Int] 2022 Jul; Vol. 33 (7), pp. 1501-1510. Date of Electronic Publication: 2022 Feb 01.
DOI: 10.1007/s00198-022-06313-1
Abstrakt: This study describes the clinical, radiological, and molecular data of four new patients with osteoporosis-pseudoglioma syndrome and assesses their response to bisphosphonate therapy.
Introduction: Osteoporosis-pseudoglioma syndrome (OPPG) is a very rare disorder characterized mainly by severe juvenile osteoporosis and congenital blindness. OPPG is caused by biallelic mutations in the gene encoding low-density lipoprotein receptor-related protein 5 (LRP5).
Methods: We present the clinical, radiological, and molecular findings of four new patients with OPPG from Egypt. We also assessed patients' response to oral and intravenous bisphosphonate therapy.
Results: All patients had reduced bone mineral density (BMD) with variable number of fractures per year, in addition to bone abnormalities and the characteristic eye phenotype associated with OPPG. Mutation analyses of LRP5 gene revealed three different homozygous variants including two novel ones, c.7delG (p.A3Qfs*80) and c.3280G > A (p.E1094K). The c.3280G > A (p.E1094K) was recurrent in two unrelated patients who shared a unique haplotype suggesting a possible founder effect. The use of bisphosphonate therapy was beneficial; however, intravenous bisphosphonate administration led to a more favorable response.
Conclusion: Our study described the phenotypic and genetic features of four patients with OPPG and identified two new LRP5 variants, thus expanding the mutational spectrum of OPPG. In addition, our study reinforces the efficiency of using intravenous bisphosphonates in the management of patients with OPPG.
(© 2022. International Osteoporosis Foundation and National Osteoporosis Foundation.)
Databáze: MEDLINE
Externí odkaz: