Li Juan, Duan Jintao, He Shuli, Li Ying, Wang Meifen, Deng Chengjun
Department of Gastroenterology, Kunming Children's Hospital, Kunming, China.
Department of Infectious Diseases, Kunming Children's Hospital, Kunming, China.
Front Pediatr. 2025 Jan 13;12:1293356. doi: 10.3389/fped.2024.1293356. eCollection 2024.
The diagnostic criteria of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) have not been established due to non-specific clinical manifestations, and our understanding on the treatment outcome is still limited. We aim to investigate the biochemical characteristics, genetic variants, and treatment outcome of NICCD patients.
We compared the nutritional status and biochemical characteristics of 55 NICCD infants and 27 idiopathic neonatal cholestasis (INC) infants. gene variant analysis was performed for definitive diagnosis of NICCD. NICCD infants received 12 months of lactose-free and/or medium-chain triglyceride-enriched (LF/MCT) formula treatment. The treatment efficacy was evaluated by comparing the outcome of NICCD with the 24 healthy infants that were selected as normal controls. All NICCD patients were followed up until death or at least 1 year of age.
Compared to INC group, significant increase was found in levels of total bilirubin, indirect bilirubin, total bile acid, gamma-glutamyl transpeptidase, alkaline phosphatase, prothrombin time, thrombin time, international normalized ratio, alpha-fetoprotein (AFP), Vitamin D, and Vitamin E of NICCD group, while alanine aminotransferase, albumin, fibrinogen, glucose, and Vitamin A levels showed significant decrease in the NICCD group ( < 0.05). There were 7 novel variants among 19 variant types. No significant differences were found between NICCD patients treated for 12 months and normal controls. In long term follow-up, 2 cases developed FTTDCD, 8 cases had special dietary habits, and 1 case died from cirrhosis.
NICCD showed more severe impairments in liver, coagulation, and metabolic function than INC. Significantly increased AFP levels could provide reference for the differential diagnosis of NICCD. The newly discovered variants may be meaningful for the individualized treatment of NICCD patients. LF/MCT formula was recommended for NICCD patients.
由于临床表现不具特异性，瓜氨酸缺乏所致新生儿肝内胆汁淤积症（NICCD）的诊断标准尚未确立，且我们对其治疗结果的了解仍很有限。我们旨在研究NICCD患者的生化特征、基因变异及治疗结果。
我们比较了55例NICCD婴儿和27例特发性新生儿胆汁淤积症（INC）婴儿的营养状况和生化特征。进行基因变异分析以明确NICCD的诊断。NICCD婴儿接受了12个月的无乳糖和/或富含中链甘油三酯（LF/MCT）配方奶治疗。通过将NICCD的治疗结果与24例被选为正常对照的健康婴儿的结果进行比较来评估治疗效果。所有NICCD患者均随访至死亡或至少1岁。
与INC组相比，NICCD组的总胆红素、间接胆红素、总胆汁酸、γ-谷氨酰转肽酶、碱性磷酸酶、凝血酶原时间、凝血酶时间、国际标准化比值、甲胎蛋白（AFP）、维生素D和维生素E水平显著升高，而NICCD组的丙氨酸氨基转移酶、白蛋白、纤维蛋白原、葡萄糖和维生素A水平显著降低（<0.05）。在19种变异类型中有7种新变异。接受12个月治疗的NICCD患者与正常对照之间未发现显著差异。在长期随访中，2例发展为FTTDCD，8例有特殊饮食习惯，1例死于肝硬化。
NICCD在肝脏、凝血和代谢功能方面的损害比INC更严重。显著升高的AFP水平可为NICCD的鉴别诊断提供参考。新发现的变异可能对NICCD患者的个体化治疗有意义。推荐NICCD患者使用LF/MCT配方奶。
