19例中国儿童脂蛋白脂肪酶缺乏症患者的临床特征、基因谱及治疗评估

Clinical profile, genetic spectrum and therapy evaluation of 19 Chinese pediatric patients with lipoprotein lipase deficiency.

作者信息

Xia Yu, Zheng Wanqi, Du Taozi, Gong Zizhen, Liang Lili, Wang Ruifang, Yang Yi, Zhang Kaichuang, Lu Deyun, Chen Xiaohong, Sun Yuning, Sun Yu, Xiao Bing, Qiu Wenjuan

机构信息

Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, School of Medicine, Shanghai Institute of Pediatric Research, Shanghai Jiao Tong University, 1665 KongJiang Road, Shanghai 200092, China (Drs Xia, Zheng, Du, Gong, Liang, Wang, Yang, Zhang, Lu, Sun, Sun, Xiao, Qiu).

Department of Endocrinology and Metabolism, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Dr Chen).

出版信息

J Clin Lipidol. 2023 Nov-Dec;17(6):808-817. doi: 10.1016/j.jacl.2023.09.012. Epub 2023 Sep 27.

DOI:10.1016/j.jacl.2023.09.012

PMID:37858495

Abstract

BACKGROUND

Lipoprotein lipase (LPL) deficiency, the most common familial chylomicronemia syndrome (FCS), is a rare autosomal recessive disease characterized by chylomicronemia and severe hypertriglyceridemia (HTG), with limited clinical and genetic characterization.

OBJECTIVE

To describe the manifestations and management of 19 pediatric patients with LPL-FCS.

METHODS

LPL-FCS patients from 2014 to 2022 were divided into low-fat (LF), very-low-fat (VLF) and medium-chain-triglyceride (MCT) groups. Their clinical data were evaluated to investigate the effect of different diets. The genotype-phenotype relationship was assessed. Linear regression comparing long-chain triglyceride (LCT) intake and TG levels was analyzed.

RESULTS

Nine novel LPL variants were identified in 19 LPL-FCS pediatric patients. At baseline, eruptive xanthomas occurred in 3/19 patients, acute pancreatitis in 2/19, splenomegaly in 6/19 and hepatomegaly in 3/19. The median triglyceride (TG) level (30.3 mmol/L) was markedly increased. The MCT group and VLF group with LCT intakes <20 en% (energy percentage) had considerably lower TG levels than the LF group (both p<0.05). The LF group presented with severe HTG and significantly decreased TG levels after restricting LCT intakes to <20 en% (p<0.05). Six infants decreased TG levels to <10 mmol/L by keeping LCT intake <10 en%. TG levels and LCT intake were positively correlated in both patients under 2 years (r=0.84) and those aged 2-9 years (r=0.89). No genotype-phenotype relationship was observed.

CONCLUSIONS

This study broadens the clinical and genetic spectra of LPL-FCS. The primary therapy for LPL-FCS pediatric patients is restricting dietary LCTs to <10 en% or <20 en% depending on different ages. MCTs potentially provide extra energy.

摘要

背景

脂蛋白脂肪酶（LPL）缺乏症是最常见的家族性乳糜微粒血症综合征（FCS），是一种罕见的常染色体隐性疾病，其特征为乳糜微粒血症和严重高甘油三酯血症（HTG），临床和基因特征有限。

目的

描述19例儿童LPL-FCS患者的临床表现及治疗情况。

方法

将2014年至2022年的LPL-FCS患者分为低脂（LF）、极低脂（VLF）和中链甘油三酯（MCT）组。评估其临床数据以研究不同饮食的效果。评估基因型与表型的关系。分析比较长链甘油三酯（LCT）摄入量与甘油三酯水平的线性回归。

结果

在19例儿童LPL-FCS患者中鉴定出9种新的LPL变异体。基线时，19例患者中有3例出现发疹性黄瘤，2例出现急性胰腺炎，6例出现脾肿大，3例出现肝肿大。甘油三酯（TG）中位数水平（30.3 mmol/L）显著升高。LCT摄入量<20%（能量百分比）的MCT组和VLF组的TG水平明显低于LF组（均p<0.05）。LF组出现严重HTG，将LCT摄入量限制在<20%（能量百分比）后TG水平显著降低（p<0.05）。6例婴儿通过将LCT摄入量保持在<10%（能量百分比），使TG水平降至<10 mmol/L。2岁以下患者（r=0.84）和2-9岁患者（r=0.89）的TG水平与LCT摄入量均呈正相关。未观察到基因型与表型的关系。