Sanna Claudia, Stéphenne Xavier, Revencu Nicole, Smets Françoise, Sassolas Agnes, Di Filippo Mathilde, Descamps Olivier S, Sokal Etienne M
Université catholique de Louvain, Cliniques Universitaires Saint Luc, Service de Gastroentérologie et Hépatologie Pédiatrique, Bruxelles, Belgium.
Université catholique de Louvain, Cliniques Universitaires Saint Luc, Centre de Génétique Humaine, Bruxelles, Belgium.
Atherosclerosis. 2016 Apr;247:97-104. doi: 10.1016/j.atherosclerosis.2016.02.009. Epub 2016 Feb 5.
Familial hypercholesterolemia (FH) is a co-dominantly inherited disorder of plasma lipoprotein metabolism. The prevalence of heterozygous FH (HeFH) is between 1/500 and 1/200 whereas that of homozygous form (HoFH) is about 1/1,000,000. Diagnosis is based on cutaneous xanthomas and untreated levels of LDL-cholesterol over 500 mg/dl before 10 years of age. Life expectancy, without treatment, does not exceed 20 years of age. The aim of this study is to characterise in details a cohort of 8 HoFH paediatric patients in order to illustrate all the current therapeutic options and to add some clinical and genetic information about this rare disease. We collected demographic, clinical, biological, imaging and genotype details. Furthermore, clinical and biochemical response to different treatment methods was retrospectively evaluated. All patients had genetically proven HoFH. All patients were subject to a lipid-lowering diet and medical treatment (except one), three patients underwent a liver transplant and one an hepatocytes infusion. Medical treatment was well tolerated with a median reduction of 44% and 47% in LDL-Cholesterol and Total Cholesterol respectively. The hepatocytes transplant produced a further, though slight, decrease in cholesterol levels as opposed to medical therapy alone. Transplanted patients normalized their cholesterol levels. Since the very high cardiovascular risk, HoFH requires immediate diagnosis, treatment and monitoring. Nowadays, the use of statins remains the cornerstone of medical therapy and liver transplantation is the possibly curative therapy. Besides, high hopes are pinned in new drugs (antibody targeting PCSK9, Mipomersen and Lomitapide) and stem cells.
家族性高胆固醇血症（FH）是一种共显性遗传的血浆脂蛋白代谢紊乱疾病。杂合子FH（HeFH）的患病率在1/500至1/200之间，而纯合子形式（HoFH）的患病率约为1/1,000,000。诊断基于皮肤黄色瘤以及10岁前未经治疗的低密度脂蛋白胆固醇水平超过500mg/dl。未经治疗的情况下，预期寿命不超过20岁。本研究的目的是详细描述一组8例HoFH儿科患者，以阐明所有当前的治疗选择，并补充有关这种罕见疾病的一些临床和遗传信息。我们收集了人口统计学、临床、生物学、影像学和基因型细节。此外，还对不同治疗方法的临床和生化反应进行了回顾性评估。所有患者均经基因证实为HoFH。所有患者均接受低脂饮食和药物治疗（除1例），3例患者接受了肝移植，1例接受了肝细胞输注。药物治疗耐受性良好，低密度脂蛋白胆固醇和总胆固醇分别中位数降低了44%和47%。与单独药物治疗相比，肝细胞移植使胆固醇水平进一步轻微下降。接受移植的患者胆固醇水平恢复正常。由于心血管风险极高，HoFH需要立即诊断、治疗和监测。如今，他汀类药物的使用仍然是药物治疗的基石，肝移植是可能的治愈性疗法。此外，人们对新药（靶向PCSK9的抗体、米泊美生和洛美他派）和干细胞寄予厚望。
