Presence of Lipid Vacuoles in Kupffer Cells as a Marker for Early Detection of Niemann-Pick Disease Type C in Neonatal Cholestasis

Abstract Background Early diagnosis of Niemann-Pick disease type C (NP-C) is the key for reduction of organ damage since a medical treatment is available now. However, early detection of patients with a high clinical suspicion of NP-C in neonatal cholestasis is still challenging. Plasma oxysterol studies demonstrate a relatively low specificity for NP-C in neonatal cholestatic patients. This study explores the significance of lipid vacuoles in Kupffer cells for early detection of NP-C in neonatal cholestasis. Results Between January 2018 and December 2020, 168 neonatal cholestatic patients with unexplained causes were underwent both liver biopsy and genetic tests, and 26 detected lipid vacuoles in Kupffer cells by CD68 staining. NP-C was diagnosed in 6 out of the 26 patients (23.1%), comparing to none of the remaining 142 neonatal cholestatic patients without vacuolar Kupffer cells (P < 0.001). In neonatal cholestatic patients with vacuolar Kupffer cells plus splenomegaly, the ratio of positive diagnosis of NP-C was 31.6% (6/19). Between January 2015 and December 2017, 3 additional NP-C patients were diagnosed. Of them, 1 patient underwent liver histologic studies also revealing lipid vacuoles in Kupffer cells. The 7 NP-C patients underwent liver biopsy at ages ranging from 35 to 112 days. Lipid vacuoles were only detected in a few Kupffer cells in the early disease course (about 1 month of age). The amount of vacuolar Kupffer cells increased with age, and the size became enlarged. Typical foam cells were only observed in HE sections of liver tissues obtained beyond 3 months of age when enlarged Kupffer cells with lipid vacuoles became obvious. In addition, 4 out of the 9 NP-C patients had fasting hypoglycemia. Conclusions Lipid vacuoles in Kupffer cells from liver biopsy can serve as a screening marker for early detection of NP-C in neonatal cholestasis.