A patient with osteoporosis, hypercholesterolemia and a novel likely pathogenic variant in the LRP5 gene. A case report

Introduction. Loss-of-function (LOF) variants of the LRP5 gene are associated with primary osteoporosis. Heterozygous carriers typically have a milder phenotype, manifested primarily by decreased bone mass in childhood. Homozygotes and compound heterozygotes for the LRP5 gene may also exhibit the phenotype of familial exudative vitreoretinopathy, which disrupts the growth and development of retinal blood vessels, and osteoporosis-pseudoglioma syndrome. Furthermore, LRP5 is essential for normal cholesterol and glucose metabolism. The impact of LRP5 gene variants on the development of atherosclerosis and its complications is controversial. On the one hand, impaired function contributes to elevated blood cholesterol levels, lipid and macrophage retention in the vascular wall, increased systemic inflammation, and osteoporosis, which itself is a risk factor for atherosclerosis. On the other hand, this pathology is characterized by the absence of plaque and aortic leaflet calcification.

Brief description. This article presents a case of a patient with osteoporosis complicated by a right tibia fracture. Genetic testing revealed a previously undescribed, likely pathogenic LOF variant in the LRP5 gene (p.Leu17ArgfsTer128). At the time of examination (at age 64), the patient had no subclinical manifestations of carotid atherosclerosis, except for increased intima-media thickness, and total coronary calcium score was 0. Six years after visit, it was learned that at age 65, she had an acute myocardial infarction and underwent transluminal balloon angioplasty with stenting of the anterior descending artery.

Conclusion. This case presents with a combination of osteoporosis complicated by a right tibia fracture and severe hypercholesterolemia, with progressive coronary atherosclerosis without plaque calcification, ultimately resulting in myocardial infarction. This patient carried a previously undescribed, likely pathogenic, LOF variant in the LRP5 gene.

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