Fornari Elena, Stefanutti Claudia, Mancioppi Valentina, Watts Gerald F, Pisciotta Livia, Morandi Anita, Maffeis Claudio
Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University of Verona, Verona, Italy (Drs Fornari, Mancioppi, Morandi, Maffeis).
Department of Molecular Medicine, Extracorporeal Therapeutic Techniques Unit, Lipid Clinic and Atherosclerosis Prevention Centre, Regional Centre for Rare Diseases, Immunohematology and Transfusion Medicine, Umberto I Hospital, "Sapienza" University of Rome, Rome, Italy (Dr Stefanutti); Multidisciplinary International Group for Hemapheresis TherapY and MEtabolic DIsorders Control (MIGHTY MEDIC.ORG), Rome, Italy (Dr Stefanutti).
J Clin Lipidol. 2025 May-Jun;19(3):689-694. doi: 10.1016/j.jacl.2025.02.012. Epub 2025 Feb 21.
The rare homozygous form of familial hypercholesterolemia (HoFH) is characterized by extremely high low-density lipoprotein (LDL) cholesterol levels, typically exceeding 13 mmol/L (500 mg/dL), and a variable phenotype that may include marked premature atherosclerotic cardiovascular disease. HoFH with null-null LDL receptor mutations can be highly resistant to standard pharmacological therapies. The standard of care treatment option is lipoprotein apheresis (LA). However, LA is not commonly available, is technically demanding, and is relatively invasive and arduous for very young patients. Here we report effective lowering of the LDL cholesterol in a 13-month-old child with HoFH treated with evinacumab, initially at a low dose (7.5 mg/kg), later increased to 15 mg/kg/28 days. The decision was made after the failure of standard drug therapies in a sibling with the same null-null mutation in the LDL receptor, submitted to liver transplantation, who had severe complications. The treatment with evinacumab was safe and effective; LDL cholesterol, triglycerides, and apolipoprotein B concentrations all decreased by over 80%. Our findings suggest that evinacumab is a safe and effective option for treating very young patients with HoFH who do not respond to conventional therapies.
家族性高胆固醇血症（HoFH）的罕见纯合子形式的特征是极低密度脂蛋白（LDL）胆固醇水平极高，通常超过13 mmol/L（500 mg/dL），以及可能包括明显的早发性动脉粥样硬化性心血管疾病的可变表型。具有无效LDL受体突变的HoFH对标准药物治疗可能具有高度抗性。护理标准治疗选择是脂蛋白分离术（LA）。然而，LA并不普遍可用，技术要求高，并且对非常年幼的患者来说相对具有侵入性且艰巨。在此，我们报告了一名13个月大的HoFH患儿使用evinacumab治疗后LDL胆固醇有效降低，最初剂量较低（7.5 mg/kg），后来增加到15 mg/kg/28天。这一决定是在一名患有相同LDL受体无效突变的同胞接受肝移植后出现严重并发症，标准药物治疗失败后做出的。使用evinacumab治疗安全有效；LDL胆固醇、甘油三酯和载脂蛋白B浓度均下降超过80%。我们的研究结果表明，evinacumab是治疗对传统疗法无反应的年幼HoFH患者的一种安全有效的选择。
