Nadyrshina D D, Khusainova R I
Ufa University of Science and Technology, Ufa, Russia.
Ufa University of Science and Technology, Ufa, Russia Saint Petersburg State University, St. Petersburg, Russia.
Vavilovskii Zhurnal Genet Selektsii. 2023 Jul;27(4):383-392. doi: 10.18699/VJGB-23-46.
Osteopetrosis ("marble bone", ICD-10-78.2) includes a group of hereditary bone disorders distinguished by clinical variability and genetic heterogeneity. The name "osteopetrosis" comes from the Greek language: 'osteo' means 'bone' and 'petrosis' means 'stone', which characterizes the main feature of the disease: increased bone density caused by imbalances in bone formation and remodeling, leading to structural changes in bone tissue, predisposition to fractures, skeletal deformities. These defects, in turn, affect other important organs and tissues, especially bone marrow and the nervous system. The disease can be autosomal recessive, autosomal dominant, X-linked or sporadic. Autosomal dominant osteopetrosis has an incidence of 1 in 20,000 newborns and autosomal recessive one has 1 in 250,000. To date, 23 genes have been described, structural changes in which lead to the development of osteopetrosis. Clinical symptoms in osteopetrosis vary greatly in their presentation and severity. The mildest skeletal abnormalities are observed in adulthood and occur in the autosomal dominant form of osteopetrosis. Severe forms, being autosomal recessive and manifesting in early childhood, are characterized by fractures, mental retardation, skin lesions, immune system disorders, renal tubular acidosis. Clinical examination and review of radiographs, bone biopsy and genetic testing provide the bases for clinical diagnosis. The early and accurate detection and treatment of the disease are important to prevent hematologic abnormalities and disease progression to irreversible neurologic consequences. Most patients die within the first decade due to secondary infections, bone marrow suppression and/or bleeding. This article summarizes the current state of the art in this field, including clinical and genetic aspects, and the molecular pathogenesis of the osteopetrosis.
骨质石化症（“大理石骨病”，国际疾病分类第十版编码：78.2）是一组遗传性骨病，其特点是临床变异性和遗传异质性。“骨质石化症”这个名称源自希腊语：“osteo”意为“骨”，“petrosis”意为“石”，这体现了该疾病的主要特征：由于骨形成和重塑失衡导致骨密度增加，进而引起骨组织结构改变、易发生骨折和骨骼畸形。这些缺陷反过来又会影响其他重要器官和组织，尤其是骨髓和神经系统。该疾病可以是常染色体隐性、常染色体显性、X连锁或散发型。常染色体显性骨质石化症在新生儿中的发病率为两万分之一，常染色体隐性骨质石化症的发病率为二十五万分之一。迄今为止，已有23个基因被描述，这些基因的结构变化会导致骨质石化症的发生。骨质石化症的临床症状在表现形式和严重程度上差异很大。最轻微的骨骼异常在成年期出现，见于常染色体显性形式的骨质石化症。严重形式为常染色体隐性，在儿童早期表现出来，其特征为骨折、智力发育迟缓、皮肤病变、免疫系统紊乱、肾小管酸中毒。临床检查、X线片复查、骨活检和基因检测为临床诊断提供依据。疾病的早期准确检测和治疗对于预防血液学异常以及疾病进展至不可逆的神经后果至关重要。大多数患者在第一个十年内死于继发感染、骨髓抑制和/或出血。本文总结了该领域的当前技术水平，包括临床和遗传方面以及骨质石化症的分子发病机制。
