Pediatric Nephrology, Faculty of Medicine, Children's and Adolescents' Hospital, University Hospital of Cologne, University of Cologne, Cologne, Germany.
Pediatr Nephrol. 2023 Feb;38(2):371-382. doi: 10.1007/s00467-022-05541-1. Epub 2022 Apr 25.
Familial hypercholesterolemia (FH) is an inherited metabolic defect leading to increased total cholesterol and low-density cholesterol (LDL) from birth onwards. Homozygous FH, presenting with clear clinical features, has a prevalence of ~ 1 per million. Prevalence of heterozygous FH is 1/500 European population. Atherosclerotic burden depends on the degree and duration of high LDL exposure. In severe cases, early detection is critical, and aggressive lipid-lowering therapies should begin in early childhood to reduce coronary heart disease risk. Pediatric therapeutic concepts correspond to adults and are orientated at LDL plasma concentration. Mean LDL plasma target value during treatment is < 135 mg/dL. Medication in childhood consists of ezetemibe, statins, resins, and PCSK-9 inhibitors, with consideration for age restrictions. Only a minority achieve the treatment target with drug therapy alone. Therapeutic apheresis for the treatment of hypercholesterolemia selectively removes lipoproteins from blood (lipid apheresis (LA)). LA has a long tradition in adult medicine and is also safely used in children by a variety of methods, if customized to special pediatric needs. LA reduces cholesterol levels independently of residual LDL-receptor function and not only achieves reduction or disappearance of xanthomas but also inhibits progression of or mitigates aortic valve stenosis and supravalvular aortic stenosis as well as coronary artery and other atherosclerotic lesions. Cardiovascular prognosis of patients with otherwise untreatable FH depends largely on timely use of LA. Taking into account LA as a lifelong treatment, starting early in childhood, it is important to accommodate therapy modalities, such as treatment frequency and point of time, into the life of the individual.
家族性高胆固醇血症（FH）是一种遗传性代谢缺陷，从出生起就会导致总胆固醇和低密度脂蛋白胆固醇（LDL）升高。表现出明显临床特征的纯合子 FH 的患病率约为每百万分之一。杂合子 FH 的患病率为欧洲人群的 1/500。动脉粥样硬化负担取决于 LDL 暴露的程度和持续时间。在严重的情况下，早期检测至关重要，应在儿童早期开始积极的降脂治疗，以降低冠心病风险。儿科治疗概念与成人相似，以 LDL 血浆浓度为导向。治疗期间平均 LDL 血浆靶值<135mg/dL。儿童药物治疗包括依折麦布、他汀类药物、树脂和 PCSK-9 抑制剂，并考虑年龄限制。只有少数患者可以通过单独药物治疗达到治疗目标。治疗性血液净化（therapeuticapheresis）用于治疗高胆固醇血症，可选择性地从血液中去除脂蛋白（脂质吸附（lipidapheresis，LA））。LA 在成人医学中已有悠久的历史，并且通过多种方法在儿童中安全使用，具体方法会根据特殊的儿科需求进行定制。LA 可降低胆固醇水平，独立于残余 LDL 受体功能，不仅可减少或消除黄瘤，还可抑制主动脉瓣狭窄和升主动脉瓣上狭窄以及冠状动脉和其他动脉粥样硬化病变的进展或减轻其严重程度。无法通过其他治疗方法治疗的 FH 患者的心血管预后在很大程度上取决于及时使用 LA。考虑到 LA 是一种终生治疗，应在儿童早期开始，因此将治疗频率和时间点等治疗方式纳入个体生活中非常重要。
