J Korean Med Sci.  2016 Jul;31(7):1168-1172. 10.3346/jkms.2016.31.7.1168.

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

Affiliations
  • 1Department of Neurology, Dong-A University College of Medicine, Busan, Korea. jwkim@dau.ac.kr
  • 2Department of Psychiatry, Dong-A University College of Medicine, Busan, Korea.
  • 3Department of Nuclear Medicine, Dong-A University College of Medicine, Busan, Korea.
  • 4Department of Laboratory Animal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea.
  • 5Department of Physiology, School of Medicine, Kyungpook National University, Daegu, 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.

Keyword

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

MeSH Terms

Abdomen/diagnostic imaging
Asian Continental Ancestry Group/genetics
Carrier Proteins/genetics
DNA Mutational Analysis
Exons
Female
Gait Disorders, Neurologic/etiology
Humans
Male
Membrane Glycoproteins/genetics
Niemann-Pick Disease, Type C/*diagnosis/genetics
Psychotic Disorders/etiology
Republic of Korea
Siblings
Tomography, X-Ray Computed
Young Adult
Carrier Proteins
Membrane Glycoproteins

Figure

  • 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.


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