ОСТЕОПЕТРОЗ

Остеопетроз («болезнь мраморной кости») – это общий термин, включающий в себя группу весьма редких наследственных заболеваний скелета, характеризующихся повышенной плотностью костей, выявляемой при рентгенографии. Встречаемость этих состояний достаточно сложно оценить, однако, считается, что частота аутосомно-рецессивного остеопетроза составляет порядка 1 к 250 000 рождаемым, тогда как аутосомно-доминантный остеопетроз – 1 к 20 000. Описываемые состояния могут значительно различаться по своим проявлениям и их выраженности. Некоторые из них дебютируют в неонатальном периоде с развитием угрожающих жизни осложнений, таких как патология костного мозга (так называемый «злокачественный» аутосомно-рецессивный остеопетроз), другие – являются лишь случайной находкой при рентгенографии (например остеопойкилоз). Классический аутосомно-рецессивный остеопетроз характеризуется переломами, низким ростом, компрессионными нейропатиями, гипокальциемией, сопровождающейся тетаническими судорогами, и угрожающей жизни панцитопенией. Наличие первичной нейродегенерации, умственной отсталости, вовлеченности кожи, иммунной системы или почечного тубулярного ацидоза может привести к более редким вариантам остеопетроза, тогда как начало первичных проявлений патологии скелета, таких как переломы и остеомиелит в позднем детстве или юности, типично для аутосомно-доминантного остеопетроза. Заболевание вызывается нарушением развития или функционирования остеокластов, и в качестве причинных были идентифицированы по крайней мере мутации 10 генов у порядка 70% пациентов. Заболевание может наследоваться по аутосомно-рецессивному, аутосомно-доминантному и сцепленному с полом путям, при этом наиболее тяжелыми формами являются аутосомно-рецессивные. Диагноз в основном основывается на оценке клинических и рентгенологических данных, подтверждаемых генетическим исследованием, когда оно доступно. Установление диагноза дает возможность понять истинную природу заболевания, назначить специфическую терапию, прогнозировать риск передачи потомству и проводить пренатальное выявление тяжелых форм. Лечение описываемой группы заболеваний в основном симптоматическое, также применяется трансплантация стволовых клеток крови при наиболее тяжелых формах, сочетающихся с поражением костного мозга, что определяет наибольшую выживаемость в этой группе. Тяжелые неонатальные формы остеопетроза сочетаются с низкой выживаемостью, большинство пациентов при отсутствии лечения умирают в первую декаду в результате подавления функции костного мозга. Продолжительность жизни при формах, манифестирующих во взрослом возрасте, – обычная. Ожидается, что более глубокое понимание патогенеза описываемых состояний на молекулярном уровне откроет новые мишени для фармакотерапии.

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