Department of Pediatrics, Unit of Rare Diseases, Giannina Gaslini Institute, Largo Gaslini 3, 16147, Genoa, Italy.
Department of Internal Medicine, University of Genoa, Viale Benedetto XV 6, 16132, Genoa, Italy.
Orphanet J Rare Dis. 2018 Jan 27;13(1):24. doi: 10.1186/s13023-018-0768-8.
Lysosomal acid lipase deficiency is an autosomal recessive metabolic disease with a wide range of severity from Wolman Disease to Cholesterol Ester Storage Disease. Recently enzyme replacement therapy with sebelipase alpha has been approved by drug agencies for treatment of this lysosomal disease. Ezetimibe is an azetidine derivative which blocks Niemann Pick C1-Like 1 Protein; as its consequence, plasmatic concentration of low density lipoproteins and other apoB-containing lipoproteins, that are the substrate of lysosomal acid lipase, are decreased. Furthermore, ezetimibe acts by blocking inflammasome activation which is the cause of liver fibrosis in steatohepatitis and in lysosomal storage diseases.
Two patients with Cholesterol Ester Storage Disease were treated with ezetimibe for 9 years and a third patients for 10 years. Treatment was supplemented with low dose of atorvastatin in the first two patients during the last 6 years. All patients showed a significant reduction of alanine aminotransferase, cholesterol and triglyceride. Furthermore, no progression of liver fibrosis was demonstrated.
In this observational case series, ezetimibe is effective, safe, and sustainable treatment for lysosomal acid lipase deficiency. Further studies are warranted to demonstrate that ezetimibe is an alternative therapy to enzyme replacement therapy.
溶酶体酸性脂肪酶缺乏症是一种常染色体隐性遗传代谢疾病，其严重程度范围广泛，从沃曼病到胆固醇酯贮积症不等。最近，酶替代疗法贝利普酶α已被药物监管机构批准用于治疗这种溶酶体疾病。依泽替米贝是一种氮杂环丁烷衍生物，可阻断尼曼匹克 C1 样蛋白 1；因此，其结果是，血浆中低密度脂蛋白和其他载脂蛋白 B 的脂蛋白的浓度降低，这些脂蛋白是溶酶体酸性脂肪酶的底物。此外，依泽替米贝通过阻断炎症小体的激活起作用，炎症小体的激活是脂肪性肝炎和溶酶体贮积病中肝纤维化的原因。
2 名胆固醇酯贮积症患者接受依泽替米贝治疗 9 年，第 3 名患者接受依泽替米贝治疗 10 年。在前 2 名患者的最后 6 年中，依泽替米贝与低剂量阿托伐他汀联合治疗。所有患者的丙氨酸氨基转移酶、胆固醇和甘油三酯均显著降低。此外，未发现肝纤维化进展。
在这项观察性病例系列研究中，依泽替米贝是治疗溶酶体酸性脂肪酶缺乏症的有效、安全且可持续的治疗方法。需要进一步的研究来证明依泽替米贝是酶替代疗法的替代疗法。
