以新生儿胆汁淤积症为首要表现的尼曼匹克病C型三例

Three Chinese children with Niemann-Pick disease type C with neonatal cholestasis as initial presentation

目的探讨以新生儿胆汁淤积症为首要表现的尼曼匹克病c型的临床特点，提高对尼曼匹克病C型的认识。方法对3例尼曼匹克病c型患儿的临床特点、实验室检查和影像学表现、基因测序结果进行回顾性分析。结果3例患儿男2例女I例，2月龄～5岁10个月，均以新生儿病理性黄疸为首发症状，黄疸轻度到中度，胆汁酸56．3-104．2μmol／L，总胆红素116．7-182．3μmol／L，直接胆红素77．8-133．1μmol／L，伴肝脾肿大，高密度脂蛋白胆固醇0．65～0．79mmol／L，其中2例X线显示双肺纹理增多。基因测序结果明确3例患儿均携带NPCI基因杂合致病突变：C．2741G〉T＋13．3020C〉G（P．C914F＋P．P1007R），C．2177G〉C＋c．3734-3735delCT（P．R726T＋P．P1245RfsX12）和c．2054T〉C＋c．2128C〉T（P．1685T＋P．Q710x），尼曼匹克病c型诊断明确。结论新生儿期出现病理性黄疸，伴胆汁淤积症和肝脾肿大者需排除尼曼匹克病c型，NPCI基因检测发现致病性突变能明确诊断。

Objective To analyze the clinical characteristics of three Chinese cases of Niemann- Pick disease type C patients with neonatal cholestasis as initial presentation, and enhance awareness of Niemann-Pick disease type C among pediatricians. Method Three sporadic cases with confirmed Niemann- Pick disease type C initially presented as neonataj cholestasis were retrospectively reviewed in this study. Their peripheral blood specimens were collected after obtaining informed consent. All exons and the intron- exon boundaries of NPC1 gene were examined by bi-directional sequencing. Result Three patients, 1 female and 2 males, aged from 2 months to 5 years and 10 months, all first complained of jaundice in the neonatal period. Laboratory tests showed total bilirubin and direct bilirubin significantly increased with predominant increase of direct bilirubin. Total bile acid, aspartate aminotransferase （AST）, and alanine aminotransferase （ALT） were also increased, while high-density lipoprotein cholesterol decreased. All patients were also accompanied by hepatosplenomegaly, with two of them having increased bronchovaseular markings in chest X-ray. Two heterozygous changes of NPC1 gene, c. 2741G 〉 T ＋ c. 3020C 〉 G （ p. C914F ＋ p. P1007R）, c. 2177G 〉 C ＋ c. 3734_3735delCT （p. R726T ＋ p. P1245RfsX12）, and c. 2054T 〉 C ＋ c. 2128C 〉 T（ p. I685T ＋ p. Q710X）, were identified in patient 1, 2 and 3, respectively. Conclusion We reported three cases suffered from Niemann-Pick disease type C with initial presentation as neonatal cholestasis in the mainland of China. For newborns with prolonged jaundice in the neonatal period, as well as neonatal cholestasis, hepatosplenomegaly, Niemann-Pick type C should be included in consideration of differential diagnosis. Genetic testing can identify causative mutations for diagnosis.