儿童家族性高胆固醇血症的治疗进展

近年来，人们逐渐认识到家族性高胆固醇血症对人体的危害，以及从儿童时期开始治疗的重要性。本语文简述儿童家族性高胆固醇血症的治疗进展，早期预防并发症的发生。     

儿童家族性高胆固醇血症的治疗进展

近年来，人们逐渐认识到家族性高胆固醇血症对人体的危害，以及从儿童时期开始治疗的重要性。本语文简述儿童家族性高胆固醇血症的治疗进展，早期预防并发症的发生。     

家族性高胆固醇血症

Fredrickson氏等将高脂蛋白血症分为5型,Beaumont氏等作了修正,规定了每一型的判断标准和诊断方法(表1)。此种分类法已被广泛接受。家族性高胆固醇血症     

纯合子家族性高胆固醇血症的治疗

在3例患有严重家族性纯合子高胆固醇血症(HFH)病人的治疗过程中证明应用葡聚糖硫酸酯分离低密度脂蛋白(LDL)能有效地降低总胆固醇和LDL胆固醇的浓度,并可以预防HFH儿童动脉粥样硬化,     

家族性高胆固醇血症一例

先证者，男，8岁5个月，因体表多处大小不等黄色肿物就诊。患儿生后即发现股部及臀部黄色线形物，并随年龄增长而增大。同时在眼睑、双侧指关节、指间隙、腕、肘、膝、踝和跟健等处先后出现大小不等、边缘不整、扁平和结节状黄瘤。体检：身高114cm，体重19kg，血压18．6／9kPa（140／68mmH），心率92次／分。可见角膜老年环。上述部位可见皮肤黄瘤（图1～2）。心尖部闻Ⅱ级收缩期吹风样杂音，肝肋下1cm，脾未及。肝功能正常。总胆固醇（T）23．8mmol／L，甘油三酯（TG）1．3mmol／L，TC／TG＝18．3；低密度脂蛋白胆固醇（LDL－oh）17…     

家族性高胆固醇血症1例

患儿，男，10岁6个月。因自幼患皮肤黄色瘤来我院就诊。生后1岁多皮肤出现黄色瘤，先是点状后逐渐融合成条索状和片状；9岁来诊时分布在肘、膝、臀部、足跟、手背处。既往未治疗过。无其他先天性疾病史。否认近亲结婚和家族遗传性病史。其弟2岁，生后1岁多时皮肤出现黄色瘤，分布在臀部、足跟、手背处，呈点状。     

家族性高胆固醇血症1例报告

男,9岁。患儿于16个月前上学途中突然胸痛、气急、心悸与出大汗,就地站立片刻后缓解。此后类似发作多次,休息后能缓解,发作后感乏力。4个月前行走途中再次发作,突然晕倒20分钟,无抽搐与大小便失禁。当地医院查血清胆固醇450mg,用能量合剂来治疗10天症状明显好转。此后发作     

家族性高胆固醇血症一家系报告

家族性高胆固醇血症一家系报告黑龙江省伊春市第二医院（１５３１００）刘玲天津医科大学附属医院（３０００５２）杨菁岩马咸成家族性高胆固醇血症是以特征性黄瘤，高胆固醇血症，早发的动脉硬化为特点。现将本症的１个家系报告如下。１病历摘要先证者男，１１岁。皮肤黄...     

家族性高胆固醇血症2例病例报道

目的 探讨家族性高胆固醇血症的临床和基因特点,提高对家族性高胆固醇血症的认识。方法 对两例家族性高胆固醇血症患儿的临床特点、实验室和影像学表现、基因测序结果进行分析,并且综合文献复习。结果 2例患儿均以皮肤黄瘤和腱黄瘤为首发症状,TC和LDL-C明显升高。LDLR基因测序结果明确2例患儿均为LDLR基因突变：1例为LDLR纯合突变,另1例为LDLR杂合突变,确诊为家族性高胆固醇血症。纯合子患儿出现角膜弓、主动脉及冠状动脉壁钙化。 结论 家族性高胆固醇血症患儿的临床特点为：皮肤黄瘤和腱黄瘤、角膜弓、血管病变,TC和LDL-C明显升高。基因测序能够发现致病突变。LDLR基因纯合突变患者降脂药物治疗效果差,必要时应行肝移植术。     

家族性高胆固醇血症一家3例报道

男,11岁。皮肤出现黄色瘤9年,发作性心前区痛1年入院。其父及弟在我院诊断为家族性高胆固醇血症。体检:Bp13.5/7kPa,四肢关节伸面数十个黄色斑块,质软。双角膜外缘有灰色环。心尖都有收缩期震颤,心界向两侧扩大,心尖部有Ⅳ级收缩     

Growth during treatment of familial hypercholesterolemia

Treatment of hypercholesterolemic children with restriction of dietary saturated fat may result in an inadequate supply of energy for normal somatic growth. We examined the growth of 30 children with familial hypercholesterolemia, some of whom were also treated with colestipol, a bile acid-binding resin. The median duration of treatment was 8.5 years in 13 patients on diet only, and 5.5 years + 3.5 years in 17 patients treated with diet followed by diet and colestipol. Statistically significant reductions in serum total cholesterol were obtained in both groups. The SD scores for both height/age and weight/age decreased by approximately 0.4 during dietary treatment (p < 0.05), but were not affected by treatment with colestipol. These results document the risk of growth retardation during dietary treatment of children with familial hypercholesterolemia.     

家族性载脂蛋白B_(100)缺陷第3500位氨基酸突变检测方法比较及初步应用

为比较和探讨家族性载脂蛋白Ｂ１００缺陷患者ａｐｏＢ－３５００位突变的检测方法，对４个高胆固醇血症家族的１９名成员，采用聚合酶链反应（ＰＣＲ）结合酶切法、等位基因特异寡核苷酸（ＡＳＯ）探针杂交法及ＰＣＲ产物序列分析法检测此点突变，并通过定点突变法构建一人工突变体作为阳性对照，以确保试验方法可靠。结果：４个家族１９名成员通过ＰＣＲ结合酶切及ＡＳＯ探针杂交两种方法皆没有检测到ａｐｏＢ－３５００位突变，与测序结果一致；测序结果验证人工构建突变体的１０６５８位核苷酸为Ａ。结论：比较而言，ＰＣＲ结合酶切法是检测ａｐｏＢ－３５００位突变的一种简便而可靠方法；通过设计适当引物在ＰＣＲ产物中引进酶切位点及构建人工阳性对照的方法，是检测点突变疾病的新思路；ａｐｏＢ－３５００位突变不是引起此４个家族成员胆固醇升高的原因。     

Long-term treatment of severe familial hypercholesterolemia in children: effect of sitosterol and bezafibrate.

Seven prepubertal children (age range 5.3 to 10.8 years) with severe heterozygous familial hypercholesterolemia (serum cholesterol concentration 416 +/- 85 mg/dL and low-density lipoprotein [LDL] cholesterol concentration 360 +/- 90 mg/dL) were first treated by dietary intervention, second by sitosterol (3 x 2 g/d), and third by bezafibrate (2 x 200 mg/d). Each treatment period lasted 3 months. Subsequently, a treatment combining half the dose of sitosterol and bezafibrate was administered for the following 24 months. Diet alone reduced total and LDL cholesterol values by 4.5% (not significant) and 6.6% (P less than .05), respectively. Sitosterol lowered total and LDL cholesterol values by 17% (P less than .05) when compared with diet alone. Compared with sitosterol, bezafibrate produced a more pronounced effect on total and LDL cholesterol values (-18% and -28%, P less than .05), and high-density lipoprotein cholesterol concentration increased significantly from 48 mg/dL to 55 mg/dL. Combined treatment with half the dose each of sitosterol and bezafibrate was as effective as the higher dose of bezafibrate, and reduction averaged almost 40% and 50% for total and LDL cholesterol values; this lipid-lowering effect persisted for the next 24 months. Laboratory safety parameters and physical examination revealed no obvious side effects. This study indicates that the combination of sitosterol (3 x 1 g/d) plus bezafibrate (1 x 200 mg/d) is an alternate, acceptable, safe, and effective therapeutic approach for treatment of severe hypercholesterolemia in children with high-risk familial hypercholesterolemia.     

Liver transplantation for homozygote familial hypercholesterolemia: the only curative treatment

FH is an autosomal dominant genetic disorder characterized by increased TC and LDL level, which leads to xanthomas, atherosclerosis, and cardiac complications even in childhood. The treatment options are diet, medical treatment, lipid apheresis, and LT. The aim of our study was to analyze our data of patients with FH. Between 2004 and 2015, there were 51 patients who underwent pediatric LT at our center. All patients with FH were identified, and the data were retrospectively analyzed. There were eight patients with homozygous FH in the median age of 10 years (IQR 6–12) who underwent LT. The median pre‐operative TC and LDL levels were 611 mg/dL (IQR: 460–844) and 574 mg/dL (IQR: 398–728) and decreased to normal levels 1 week after LT (TC: 193 mg/dL and LDL: 141 mg/dL). Two patients died two and 18 months after LT due to sudden cardiac arrest. Both patients were diagnosed with cardiovascular disease pre‐operatively. The LT is the only curative treatment for this disease. To achieve an excellent outcome, it should be performed before the development of cardiovascular disease, because the regression of severe cardiovascular disease after transplantation is limited.     

Serum noncholesterol sterols in children with heterozygous familial hypercholesterolemia undergoing pravastatin therapy

OBJECTIVE: To assess causes for insufficient cholesterol-lowering response to pravastatin and plant stanol esters in children with heterozygous familial hypercholesterolemia (HeFH). STUDY DESIGN: Nine of 16 children with HeFH who had not reached normocholesterolemia (< or =194 mg/dL [< or =5 mmol/L]) by 1 year after treatment (40 mg pravastatin and plant stanol ester) were called nonresponders. The 7 remaining children were responders. Serum noncholesterol sterol ratios (10(2) x mmol/mol of cholesterol), surrogate estimates of cholesterol absorption (cholestanol, campesterol, sitosterol) and synthesis (desmosterol and lathosterol), were studied at study baseline (on plant stanol esters) and during combination therapy with pravastatin and plant stanol esters. RESULTS: Pravastatin decreased the serum levels of cholesterol and cholesterol synthesis markers, and increased the ratios of cholesterol absorption markers. Compared with the responders, the nonresponders had higher study baseline (on plant stanol esters) serum cholesterol concentrations (299 +/- 39 vs 251 +/- 35 mg/dL [7.7 +/- 1.0 vs 6.5 +/- 0.9 mmol/L]; P <.001) and higher respective ratios of campesterol (371 +/- 99 vs 277 +/- 67 10(2) x mmol/mol of cholesterol; P = .049) and sitosterol (176 +/- 37 vs 126 +/- 24 10(2) x mmol/mol of cholesterol; P = .008). The higher the ratio of cholestanol at study baseline, the smaller the 1-year percent reduction in cholesterol (r = .556; P = .025). CONCLUSIONS: Pravastatin treatment increases the markers of cholesterol absorption and decreases those of cholesterol synthesis in HeFH during simultaneous inhibition of cholesterol absorption. Combined inhibition of cholesterol absorption and synthesis may not normalize serum lipids in those patients with the highest cholesterol levels, especially if signs of enhanced cholesterol absorption are detectable.     

The apolipoprotein epsilon4 allele confers additional risk in children with familial hypercholesterolemia

Children with familial hypercholesterolemia (FH) exhibit substantial variance of LDL cholesterol. In previous studies, family members of children with FH were included, which may have influenced results. To avoid such bias, we studied phenotype in 450 unrelated children with FH and in 154 affected sib-pairs. In known families with classical FH, diagnosis was based on plasma LDL cholesterol above the age- and gender-specific 95th percentile. Girls had 0.47 +/- 0.15 mmol/L higher LDL cholesterol, compared with boys (p = 0.002). Also in girls, HDL cholesterol increased by 0.07 +/- 0.03 mmol/L per 5 y (pfor trend = 0.005); this age effect was not observed in boys. The distribution of apolipoprotein (apo) E genotypes was not significantly different between probands, their paired affected siblings, or a Dutch control population. Carriers with or without one epsilon4 allele had similar LDL and HDL cholesterol levels. Within the affected sib-pairs, the epsilon4 allele explained 72.4% of the variance of HDL cholesterol levels (-0.15 mmol/L, 95% confidence interval -0.24 to -0.05, p = 0.003). The effect of apoE4 on HDL cholesterol differed with an analysis based on probands or on affected sib-pairs. The affected sib-pair model used adjustment for shared environment, type of LDL receptor gene mutation, and a proportion of additional genetic factors and may, therefore, be more accurate in estimating effects of risk factors on complex traits. We conclude that the epsilon4 allele was associated with lower HDL cholesterol levels in an affected sib-pair analysis, which strongly suggests that apoE4 influences HDL cholesterol levels in FH children. Moreover, the strong association suggests that apoE4 carries an additional disadvantage for FH children.