Yerushalmi Baruch, Sokol Ronald J, Narkewicz Michael R, Smith Debra, Ashmead Josephine W, Wenger David A
Pediatric Liver Center and Liver Transplantation Program, Department of Pediatrics, University of Colorado School of Medicine and the Children's Hospital, Denver, Colorado 80218, USA.
J Pediatr Gastroenterol Nutr. 2002 Jul;35(1):44-50. doi: 10.1097/00005176-200207000-00011.
To determine the frequency of Niemann-Pick disease type C (NPC) among children being evaluated for neonatal cholestasis during a 2-year period.
Medical records were reviewed from all infants with cholestasis and all patients with NPC evaluated at our center from January 1997 through December 1998.
Forty neonates with cholestasis were evaluated, including three patients diagnosed with NPC (age at diagnosis, 5-21 months) who were originally labeled as having idiopathic neonatal cholestasis (INH). Two adolescents (ages 14 and 16 years) were also diagnosed with NPC during this period, one who originally had neonatal hepatitis and cirrhosis, and the other who had hepatosplenomegaly throughout childhood. Three of the patients with NPC were Hispanic. At time of NPC diagnosis, infants had mildly delayed motor development and persistent splenomegaly with or without hepatomegaly, and the adolescents had ataxia, dysarthria, hepatosplenomegaly, and paresis of vertical gaze. The diagnosis of NPC was established by demonstrating defective cellular cholesterol esterification in cultured skin fibroblasts in three patients and a specific genetic mutation in three patients. Niemann-Pick disease type C was found in 27% of infants initially diagnosed with INH and 8% of all infants evaluated for cholestasis.
Niemann-Pick disease type C should be considered in all infants with cholestasis, particularly those with splenomegaly or who are of Hispanic descent. Electron microscopy and lipid analysis of liver biopsy specimens obtained during the evaluation of neonatal cholestasis may suggest this diagnosis.
确定在为期2年的新生儿胆汁淤积评估中尼曼-匹克病C型（NPC）在儿童中的发病率。
回顾了1997年1月至1998年12月在我们中心接受评估的所有胆汁淤积婴儿和所有NPC患者的病历。
评估了40例胆汁淤积新生儿，其中3例被诊断为NPC（诊断时年龄为5 - 21个月），最初被标记为特发性新生儿胆汁淤积（INH）。在此期间，还有2名青少年（年龄分别为14岁和16岁）被诊断为NPC，其中1名最初患有新生儿肝炎和肝硬化，另1名在整个儿童期都有肝脾肿大。3例NPC患者为西班牙裔。在NPC诊断时，婴儿有轻度运动发育迟缓，伴有或不伴有肝肿大的持续性脾肿大，青少年有共济失调、构音障碍、肝脾肿大和垂直凝视麻痹。通过在3例患者的培养皮肤成纤维细胞中证实细胞胆固醇酯化缺陷以及在3例患者中发现特定基因突变来确诊NPC。在最初诊断为INH的婴儿中，NPC的发病率为27%，在所有接受胆汁淤积评估的婴儿中为8%。
所有胆汁淤积婴儿，尤其是有脾肿大或西班牙裔血统的婴儿，都应考虑尼曼-匹克病C型。在评估新生儿胆汁淤积期间获取的肝活检标本的电子显微镜检查和脂质分析可能提示该诊断。
