Two Siblings with Adolescent/Adult Onset Niemann-Pick Disease Type C in Korea

Abstract

Niemann-Pick disease, type C (NP-C), is caused by NPC1 or NPC2 gene mutations. Progressive neurological, psychiatric, and visceral symptoms are characteristic. Here, we present cases of a brother (Case 1) and sister (Case 2) in their mid-20s with gait disturbance and psychosis. For the Case 1, neurological examination revealed dystonia, ataxia, vertical supranuclear-gaze palsy (VSGP), and global cognitive impairment. Case 2 showed milder, but similar symptoms, with cortical atrophy. Abdominal computed tomography showed hepatosplenomegaly in both cases. NPC1 gene sequencing revealed compound heterozygote for exon 9 (c.1552C>T [R518W]) and exon 18 (c.2780C>T [A927V]). Filipin-staining tests were also positive. When a young patient with ataxia or dystonia shows VSGP, NP-C should be considered.

Keywords: Ataxia; Dystonia; Hepatosplenomegaly; Niemann-Pick Disease, Type C; Oculomotor Paralysis; Psychosis.

Fig. 1

¹⁸F-FP-CIT PET scan of Case 1. Image shows mildly decreased ¹⁸F-FP-CIT uptake in the right putamen.

Fig. 2

Abdominal CT scan. (A) Case 1. (B) Case 2. Hepatosplenomegaly is shown in both cases, with greater prominence in Case 2.

Fig. 3

Unesterified cellular cholesterol fluorescence microscopy after filipin staining. Images are shown for: normal control subject (A), typical patient with NP-C (B), Case 1 (C), and Case 2 (D). Compared with controls, both cases show distinct cholesterol accumulation. Human NPC1-mutant and control fibroblasts (GM03123 and GM05399, respectively) were acquired from the Coriell Institute.