目的:描述Niemann-PickC型疾病(NP-C)患者的临床特征和肝脏受累过程,严重的溶酶体贮积症.
方法:回顾性纳入6个月前遗传证实为NP-C(NPC1,n=31;NPC2,n=3)和肝脏受累的患者。临床,实验室测试,和影像学数据收集,直到最后一次随访或死亡;可用的肝活检标本使用抗CD68免疫染色研究。
结果:在初始评估时(中位年龄,17天的生活),所有病人都有肝肿大,33有脾肿大,30例新生儿胆汁淤积。9例和4例患者发生门脉高压和肝功能衰竭,分别。肝活检研究,在16名患者中进行,在所有16个和15个CD68+储存细胞中显示出显著的纤维化。21例患者的血清甲胎蛋白浓度在17例中升高。16名患者的血浆氧固醇浓度增加。四名病人在六个月内死亡,包括3个肝脏受累。在存活超过6个月的患者中(中位随访,6.1年),胆汁淤积消退,除1例患者外,所有患者的门静脉高压均消退;25例患者出现神经系统受累,16例患者死亡。
结论:NP-C的肝脏受累包括短暂性新生儿胆汁淤积伴肝脾肿大,与肝纤维化有关,并导致9%的患者死亡。肝脏抗CD68免疫染色的组合,血清甲胎蛋白测定,血浆生物标志物的研究应有助于NP-C的早期鉴定。
To describe the clinical features and course of liver involvement in a cohort of patients with Niemann-Pick type C disease (NP-C), a severe lysosomal storage disorder.
Patients with genetically confirmed NP-C (
NPC1, n = 31; NPC2, n = 3) and liver involvement before age 6 months were retrospectively included. Clinical, laboratory test, and imaging data were collected until the last follow-up or death; available liver biopsy specimens were studied using anti-CD68 immunostaining.
At initial evaluation (median age, 17 days of life), all patients had hepatomegaly, 33 had splenomegaly, and 30 had neonatal cholestasis. Portal hypertension and liver failure developed in 9 and 4 patients, respectively. Liver biopsy studies, performed in 16 patients, revealed significant fibrosis in all 16 and CD68+ storage cells in 15. Serum alpha-fetoprotein concentration measured in 21 patients was elevated in 17. Plasma oxysterol concentrations were increased in the 16 patients tested. Four patients died within 6 months of life, including 3 from liver involvement. In patients who survived beyond age 6 months (median follow-up, 6.1 years), cholestasis regressed in all, and portal hypertension regressed in all but 1; 25 patients developed neurologic involvement, which was fatal in 16 patients.
Liver involvement in NP-C consisted of transient neonatal cholestasis with hepatosplenomegaly, was associated with liver fibrosis, and was responsible for death in 9% of patients. The combination of liver anti-CD68 immunostaining, serum alpha-fetoprotein measurement, and studies of plasma biomarkers should facilitate early identification of NP-C.