Kelly D A, Portmann B, Mowat A P, Sherlock S, Lake B D
Liver Unit, Children's Hospital, Birmingham, United Kingdom.
J Pediatr. 1993 Aug;123(2):242-7. doi: 10.1016/s0022-3476(05)81695-6.
The records of 52 children with Niemann-Pick disease type C were reviewed to establish whether the disease process and outcome varied with the initial clinical pattern; 34 children (65%) had cholestatic liver disease and hepatosplenomegaly in infancy; 18 were seen at a mean age of 4 years with splenomegaly or neurologic disease or both. Of the 34 children with early cholestatic liver disease, three died in the neonatal period; cholestasis and hepatomegaly subsided in the remaining 31 children, although splenomegaly persisted. Of these 31 children, 15 had persistent liver disease with elevated aminotransferase values. Serial liver biopsy specimens showed that 3 of the 15 children had normal architecture and 12 had hepatic fibrosis, with progression to cirrhosis in 5. No other significant morbidity or additional deaths were associated with the liver disease. The clinical importance of persistent liver disease was overshadowed by the subsequent development of severe neurologic disease. There was no difference in the age at onset of the disease (mean, 4.5 years) or in the pattern of neurologic disease, including supranuclear ophthalmoplegia, whether or not the child had early liver disease. Overt neurologic disease has not yet developed in seven surviving children with liver disease at onset. Sixty-seven percent of children died during the study; the main cause of death was bronchopneumonia. We conclude that the diagnosis of Niemann-Pick disease type C should be considered in patients with unexplained neonatal hepatitis, especially if splenomegaly is a persistent feature. Because liver biopsy specimens may not demonstrate storage cells, bone marrow aspiration to detect the characteristic storage cells is recommended in such patients.
回顾了52例C型尼曼-匹克病患儿的记录，以确定疾病进程和结局是否因初始临床模式而异；34例患儿（65%）在婴儿期出现胆汁淤积性肝病和肝脾肿大；18例患儿平均在4岁时出现脾肿大或神经系统疾病或两者皆有。在34例早期胆汁淤积性肝病患儿中，3例在新生儿期死亡；其余31例患儿的胆汁淤积和肝肿大消退，尽管脾肿大持续存在。在这31例患儿中，15例有持续性肝病，转氨酶值升高。连续肝活检标本显示，15例患儿中有3例结构正常，12例有肝纤维化，其中5例进展为肝硬化。没有其他严重的发病情况或额外死亡与肝病相关。持续性肝病的临床重要性被随后严重神经系统疾病的发展所掩盖。无论患儿是否有早期肝病，疾病发病年龄（平均4.5岁）或神经系统疾病模式（包括核上性眼肌麻痹）均无差异。7例起病时有肝病的存活患儿尚未出现明显的神经系统疾病。67%的患儿在研究期间死亡；主要死亡原因是支气管肺炎。我们得出结论，对于不明原因的新生儿肝炎患者，尤其是脾肿大持续存在的患者，应考虑C型尼曼-匹克病的诊断。由于肝活检标本可能无法显示贮积细胞，建议对这类患者进行骨髓穿刺以检测特征性贮积细胞。
