Zhang Y Q, Wu L T, Cheng Y, Lu Y, Li Y C, Feng J Y, Xing Q H, Li W J, Wang J S
Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai 201102, China.
Department of Clinic Nutrition, Jiangxi Provincial Children's Hospital, Nanchang 330038, China.
Zhonghua Er Ke Za Zhi. 2024 Jun 2;62(6):565-570. doi: 10.3760/cma.j.cn112140-20240301-00138.
To summarize the genotype and clinical characteristics of chylomicron retention disease (CMRD) caused by secretion associated Ras related GTPase 1B (SAR1B) gene variations. Clinical data and genetic testing results of 2 children with CMRD treated at Children's Hospital of Fudan University and Jiangxi Provincial Children's Hospital from May 2022 to July 2023 were summarized. To provide an overview of the clinical and genetic characteristics of CMRD caused by SAR1B gene variations, all of the literature was searched and reviewed from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China VIP database, China Biology Medicine disc and PubMed database (up to January 2024) with "chylomicron retention disease" "Anderson disease" or "Anderson syndrome" as the search terms. All relevant literatures were reviewed to summarize the clinical and genetic features of CMRD caused by SAR1B gene variations. One 11-year-old boy and one 4-month-old girl with CMRD. Both patients had lipid malabsorption, failure to thrive, decreased cholesterol, elevated transaminase and creatine kinase, and Vitamin E deficiency, with homozygous variations (c.224A>G) and compound heterozygous variations (c.224A>G and c.554G>T) in SAR1B gene, respectively. Case 1 was followed up for over a month, and he still occasionally experienced lower limb muscle pain. Case 2 was followed up for more than a year, and her had caught up to normal levels. Both patients had no other significant discomfort. Literature search retrieved 0 Chinese literature and 22 English literatures. In addition to the 2 cases reported in this study, a total of 51 patients were identified as CMRD caused by SAR1B gene variations. Twenty-one types of SAR1B variants 10 missense, 4 nonsense, 3 frameshift, 1 in-frame deletion, 1 splice, 1 gross deletion, and 1 gross insertion-deletion were found among the 51 CMRD cases. Among all the patients, 49 cases had lipid malabsorption (43 cases had diarrhea or fatty diarrhea, 17 cases had vomiting, and 12 cases had abdominal distension), 45 cases had lipid soluble Vitamin deficiency (43 cases had Vitamin E deficiency, 10 cases had Vitamin A deficiency, 9 case had Vitamin D deficiency, and 5 cases had Vitamin K deficiency), 35 cases had failure to thrive, 32 cases had liver involvement (32 cases had elevated transaminases, 5 cases had fatty liver, and 3 cases had hepatomegaly), 29 cases had white small intestinal mucosa under endoscopy, and 17 cases had elevated creatine kinase, 14 cases had neuropathy, 5 cases had ocular lesions, 2 cases had acanthocytosis, 1 case had decreased cardiac ejection fraction, and 1 case was symptom-free. Early infancy failure to thrive and lipid malabsorption are common issues for CMRD patients. The laboratory tests are characterized by hypocholesterolemia with or without fat-soluble Vitamin deficiency, elevated liver enzymes and (or) creatine kinase. Currently, missense variations are frequent among the primarily homozygous SAR1B genotypes that have been described.
总结由分泌相关Ras相关GTP酶1B（SAR1B）基因变异引起的乳糜微粒滞留病（CMRD）的基因型和临床特征。总结2022年5月至2023年7月在复旦大学附属儿科医院和江西省儿童医院接受治疗的2例CMRD患儿的临床资料和基因检测结果。为概述由SAR1B基因变异引起的CMRD的临床和遗传特征，以“乳糜微粒滞留病”“安德森病”或“安德森综合征”为检索词，在中国知网、万方数据知识服务平台、维普数据库、中国生物医学文献数据库和PubMed数据库（截至2024年1月）中检索并回顾了所有文献。对所有相关文献进行综述，以总结由SAR1B基因变异引起的CMRD的临床和遗传特征。1例11岁男孩和1例4个月大女孩患有CMRD。两名患者均有脂肪吸收不良、生长发育迟缓、胆固醇降低、转氨酶和肌酸激酶升高以及维生素E缺乏，SAR1B基因分别存在纯合变异（c.224A>G）和复合杂合变异（c.224A>G和c.554G>T）。病例1随访1个多月，仍偶尔出现下肢肌肉疼痛。病例2随访1年多，已恢复至正常水平。两名患者均无其他明显不适。文献检索获得0篇中文文献和22篇英文文献。除本研究报告的2例病例外，共鉴定出51例由SAR1B基因变异引起的CMRD。在51例CMRD病例中发现了21种类型的SAR1B变异，其中10种错义变异、4种无义变异、3种移码变异、1种框内缺失、1种剪接变异、1种大片段缺失和1种大片段插入缺失。在所有患者中，49例有脂肪吸收不良（43例有腹泻或脂肪泻，17例有呕吐，12例有腹胀），45例有脂溶性维生素缺乏（43例有维生素E缺乏，1例有维生素A缺乏，9例有维生素D缺乏，5例有维生素K缺乏），35例有生长发育迟缓，32例有肝脏受累（32例转氨酶升高，5例有脂肪肝，3例有肝肿大），29例在内镜检查下小肠黏膜呈白色，17例肌酸激酶升高，14例有神经病变，5例有眼部病变，2例有棘红细胞增多症，1例心脏射血分数降低，1例无症状。婴儿早期生长发育迟缓和脂肪吸收不良是CMRD患者的常见问题。实验室检查的特征是低胆固醇血症，伴或不伴有脂溶性维生素缺乏、肝酶升高和（或）肌酸激酶升高。目前，在已描述的主要纯合SAR1B基因型中，错义变异较为常见。
