Wang Jun, Sun Xinrong, Jiao Lianying, Xiao Zhengtao, Riaz Farooq, Zhang Yufeng, Xu Pengfei, Liu Ruiqing, Tang Tiantian, Liu Meiqi, Li Dongmin
Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Second Department of Infectious Disease, Children's Hospital Affiliated to Xi'an Jiaotong University, Xi'an, China.
Front Genet. 2022 Aug 16;13:916672. doi: 10.3389/fgene.2022.916672. eCollection 2022.
Our study aims to summarize and analyze the clinical characteristics of transient infantile hypertriglyceridemia (HTGTI) and variants in the glycerol-3-phosphate dehydrogenase 1 () gene and the effect of HTGTI on the protein structure of . Retrospective analysis, using the general data, symptoms, signs, and auxiliary examinations, was performed on patients with HTGTI, which were confirmed by genetic testing in our hospital and reported cases online. The clinical data were analyzed using statistical and bioinformatic approaches. A total of 31 genetically confirmed HTGTI patients were collected from our hospital and cases reported in the literature. The clinical manifestations showed the median age of onset was 6.0 (1.9, 12.0) months. All the patients had normal psychiatric status, but 22.6% of them presented growth retardation and short stature, 93.5% had hepatomegaly, and 16.1% had splenomegaly. Just a few children were reported with jaundice, cholestasis, and obesity (3.2-6.5%). The laboratory investigations showed that 96.8% of them had hypertriglyceridemia (HTG) with a median level of 3.1 (2.1, 5.5) mmol/L, but only 30.0% had returned to normal during follow-up. In addition, 93.5% of patients had elevated alanine aminotransferase (ALT) with an average level of 92.1 ± 43.5 U/L, while 38.7% had hypercholesterolemia. Upon abdominal imaging, all patients presented fatty liver and liver steatosis, with 66.7% of patients showing hepatic fibrosis. Statistical differences in triglyceride (TG) level were observed in the ≤6 months group compared with the older groups and in the 13 months to 6 years group with >6 years group ( = 22.02, < 0.05). The restricted cubic spline model showed that severe HTG decreased in the early stage of infants to the normal level; however, it rebounded again to a mild or moderate level after the following days. The genetic test revealed that the main variant types of the gene were missense variants (51.6%), followed by splicing variants (35.5%) and nonsense variants (12.9%). Of patients, 87.1% had homozygous variants, with the most frequent loci being c.361-1G > C and c.895G > A. The common manifestations of HTGTI were HTG, hepatomegaly, elevated liver transaminases, and hepatic steatosis in early infancy. However, the recurrence of aberrant HTG may pose long-term detrimental effects on HTGTI patients.
我们的研究旨在总结和分析短暂性婴儿高甘油三酯血症（HTGTI）的临床特征、甘油-3-磷酸脱氢酶1（）基因的变异以及HTGTI对该基因蛋白质结构的影响。采用回顾性分析方法，利用我院经基因检测确诊的HTGTI患者以及网上报道的病例的一般资料、症状、体征和辅助检查结果进行分析。采用统计学和生物信息学方法对临床数据进行分析。我们从我院收集了31例经基因确诊的HTGTI患者以及文献报道的病例。临床表现显示，发病年龄中位数为6.0（1.9，12.0）个月。所有患者精神状态正常，但22.6%的患者存在生长发育迟缓及身材矮小，93.5%的患者有肝肿大，16.1%的患者有脾肿大。仅有少数儿童有黄疸、胆汁淤积和肥胖（3.2 - 6.5%）。实验室检查显示，96.8%的患者有高甘油三酯血症（HTG），中位数水平为3.1（2.1，5.5）mmol/L，但随访期间仅有30.0%恢复正常。此外，93.5%的患者丙氨酸转氨酶（ALT）升高，平均水平为92.1±43.5 U/L，38.7%的患者有高胆固醇血症。腹部影像学检查显示，所有患者均有脂肪肝和肝脏脂肪变性，66.7%的患者有肝纤维化。≤6个月组与年龄较大组以及13个月至6岁组与>6岁组相比，甘油三酯（TG）水平存在统计学差异（=22.02，<0.05）。受限立方样条模型显示，婴儿早期严重的HTG水平下降至正常水平；然而，随后几天又反弹至轻度或中度水平。基因检测显示，该基因的主要变异类型为错义变异（51.6%），其次是剪接变异（35.5%）和无义变异（12.9%）。87.1%的患者有纯合变异，最常见的位点为c.361-1G>C和c.895G>A。HTGTI的常见表现为婴儿早期的HTG、肝肿大、肝转氨酶升高和肝脂肪变性。然而，异常HTG的复发可能对HTGTI患者产生长期有害影响。
