1 Science and Education Office, Jinan University, First Affiliated Hospital, Guangzhou 510630, China.
2 Department of Endocrinology and Metabolism, Jinan University, First Affiliated Hospital, Guangzhou 510630, China.
Exp Biol Med (Maywood). 2017 Jun;242(12):1271-1278. doi: 10.1177/1535370217710918. Epub 2017 May 18.
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a hereditary metabolic disease arising from biallelic mutations of SLC25A13. This study aimed to explore the characteristics of fasting blood glucose (FBG), fasting insulin (FINS) and C-peptide (C-P) levels in NICCD infants, analyze their SLC25A13 genetic mutations and further discuss the correlation between SLC25A13 genetic mutations and biochemical changes. Seventy-two cases of infants with cholestasis disease were gathered. Among them, 36 cases with NICCD diagnosis were case group. Meanwhile, 36 cases with unknown etiology but excluded NICCD were control group. FBG, FINS, C-P, ALT, AST, GGT, ALP, TG, HDL-C, LDL-C and Non-HDL-C were collected from all subjects, and DNA was extracted from venous blood for SLC25A13 mutations detection. The incidence of hypoglycemia was 3% in NICCD group. There were no significant statistical difference of FBG, FINS and C-P between NICCD and INC groups ( P > 0.05). ALT, LDL-C and Non-HDL-C levels in NICCD group were lower than the INC group, while SLC25A13 mutations were associated with the level of GGT ( P < 0.05). Ten different SLC25A13 genetic mutations were detected, among which, 851del4, IVS16ins3kb, IVS6+5 G > A and 1638ins23 mutations made up 82% of all mutations. The incidence of hypoglycemia may be higher in small gestational age infants with NICCD. Low LDL-C may be one of the characteristics of dyslipidemia in NICCD infants. There was a correlation between SLC25A13 gene mutations distribution and the GGT level, but the meaning of this finding remains to be further in-depth study. Impact statement This study aims to compare FBG, FINS, C-P, other biochemical and clinical manifestations between NICCD and non-NICCD infants, and discuss differential diagnosis of NICCD and INC beyond the genetic analysis. And investigate the correlation between SLC25A13 genetic mutations and biochemical changes. This work presented that incidence of hypoglycemia may be higher in small gestational age infants with NICCD. Low LDL-C may be one of the characteristics of dyslipidemia in NICCD infants. There was a correlation between SLC25A13 gene mutations distribution and the GGT level.
新生儿肝内胆汁淤积症由 citrin 缺乏引起（NICCD）是一种遗传性代谢疾病，由 SLC25A13 的双等位基因突变引起。本研究旨在探讨 NICCD 婴儿空腹血糖（FBG）、空腹胰岛素（FINS）和 C 肽（C-P）水平的特征，分析其 SLC25A13 基因突变，并进一步探讨 SLC25A13 基因突变与生化变化的相关性。共收集 72 例胆汁淤积症患儿，其中 36 例 NICCD 诊断为病例组，同时选择 36 例病因不明但排除 NICCD 的患儿为对照组。收集所有受试者的 FBG、FINS、C-P、ALT、AST、GGT、ALP、TG、HDL-C、LDL-C 和非 HDL-C，并从静脉血中提取 DNA 进行 SLC25A13 基因突变检测。NICCD 组低血糖发生率为 3%。NICCD 组与 INC 组 FBG、FINS 和 C-P 无统计学差异（P>0.05）。NICCD 组 ALT、LDL-C 和非 HDL-C 水平低于 INC 组，而 SLC25A13 突变与 GGT 水平相关（P<0.05）。共检测到 10 种不同的 SLC25A13 基因突变，其中 851del4、IVS16ins3kb、IVS6+5G>A 和 1638ins23 突变占所有突变的 82%。NICCD 低血糖的发生率可能在小胎龄儿中更高。NICCD 婴儿的低 LDL-C 可能是血脂异常的特征之一。SLC25A13 基因突变分布与 GGT 水平之间存在相关性，但这一发现的意义仍有待进一步深入研究。
