Korean J Gastroenterol.  2021 Oct;78(4):240-244. 10.4166/kjg.2021.079.

Niemann-Pick Disease Type C Diagnosed Using Neonatal Cholestasis Gene Panel

• Park SW
• Park JH
• Moon HJ
• Shin M
• Moon JS
• Ko JS

• KMID: 2521499
• DOI: http://doi.org/10.4166/kjg.2021.079

Abstract

Niemann-Pick disease type C (NPC) is a neurovisceral lysosomal storage disorder caused by mutations in the NPC1 and NPC2 genes. These mutations cause the accumulation of unesterified cholesterol and other lipids in the lysosomes. NPC has a broad spectrum of clinical manifestations, depending on the age of onset. A 15-day-old infant presented at the Seoul National University Children's Hospital with neonatal cholestasis and hepatosplenomegaly, with the onset of jaundice at 5 days of age. Despite supportive treatment, the patient was considered for a liver transplant because of progressive liver failure. Unfortunately, the patient died from gastrointestinal bleeding before undergoing the transplant. The neonatal cholestasis gene panel revealed two novel likely pathogenic variants in the NPC1 gene (c.1145C>G [p.Ser382*] and c.2231_2233del [p.Val744del]). The patient was diagnosed with NPC, and both parents were found to be carriers of each variant. In infants presenting with neonatal cholestasis, a gene panel can help diagnose NPC.

Keyword

Lysosomal storage diseases; NPC1; Infant; newborn; Cholestasis

Figure

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  Fig. 1 Magnetic resonance imaging of the liver revealed hepatosplenomegaly, periportal edema, and a tortuous portal vein without obstruction.

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  Fig. 2 Liver biopsy: (A) H&E staining (×400) shows marked bile duct proliferation with intracytoplasmic and canalicular cholestasis. (B) Cytokeratin 7 (CK7) staining (×200) shows a moderate ductular reaction. (C) Masson’s trichrome (M-T) staining (×400) shows periportal and pericellular fibrosis, hepatocyte ballooning, and giant cell transformation.

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