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. 2022 Sep 8:12:28.
doi: 10.5334/tohm.701. eCollection 2022.

Spectrum of Movement Disorders in Niemann-Pick Disease Type C

Rashmi Devaraj  1 , Rohan R Mahale  1 , D M Sindhu  1 , Albert Stezin  1 , Nitish Kamble  1 , Vikram V Holla  1 , M Netravathi  1 , Ravi Yadav  1 , Pramod Kumar Pal  1
Affiliations

Spectrum of Movement Disorders in Niemann-Pick Disease Type C

Rashmi Devaraj et al. Tremor Other Hyperkinet Mov (N Y). .

Abstract

Introduction: Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lipid storage disorder caused by mutations in the NPC 1 or 2 genes. Movement disorders can occur as the first symptom and as predominant symptom mainly in juvenile-onset. The frequency and heterogeneity of movement disorders in NPC are not well described. We studied the frequency and spectrum of movement disorders in patients with NPC of different age of onset.

Methods: Retrospective chart review of patients with NPC diagnosed based on the Suspicion Index tool and demonstration of foamy macrophages/sea-blue histiocytes in bone marrow aspirate.

Results: We report 9 cases of NPC with 2 patients of late-infantile, 4 juvenile-onset and 3 of adult-onset. The mean age at onset of symptoms was 11.7 ± 10.4 (range 4-38 years) and the median duration of illness was 4 years. Vertical supranuclear gaze palsy (VSGP) was noted in 8 patients and VSGP with slowing of saccade in 1 patient. Splenomegaly was seen in 5 patients. Movement disorders as the first symptom occurred in 4 patients. Dystonia was the first symptom in 2 patients and cerebellar ataxia in 2 patients. Cerebellar ataxia occurred during the course of illness in 5 patients, dystonia in 6 patients. One patient with late-infantile NPC had stimulus-sensitive myoclonus.

Conclusion: Movement disorders are common in NPC and occur as a presenting symptom. Cerebellar ataxia and dystonia are the most common movement disorder in NPC. Vertical supranuclear gaze palsy along with the movement disorders should lead to clinical suspicion of NPC.

Keywords: Niemann-Pick Type C; cerebellar ataxia; dystonia; movement disorders; sphingolipidoses; supranuclear gaze palsy.

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Conflict of interest statement

The authors have no competing interests to declare.

Figures

Brain MRI images of Patient-1 and Patient-6 with late-infantile NPC
Figure 1
Brain MRI of 2 patients with late-infantile onset NPC (A-F); (A–C) Fluid-attenuated inversion recovery (FLAIR) axial images showing periventricular hyperintense signals (red arrow); (D) axial T1-weighted image showing normal cerebellum (red arrow); (E, F) Axial T2-weighted image showing periventricular hyperintense signals and fronto-temporal atrophy (red arrow); (G) Axial T1-weighted image of juvenile-onset NPC showing right lateral frontal atrophy (red arrow).
Brain MRI images of Patient-2 with adult NPC
Figure 2
Brain MRI of patients with adult-onset NPC; Patient no 2 (A) Sagittal T2-weighted image showing cerebellar atrophy (red arrow); Patient no 3 (B, C)- (B) Axial T1-weighted image showing frontal atrophy with prominent ex-vacuo dilation of lateral ventricles (red arrow); (C) Axial T2-weighted image showing bilateral temporal atrophy and cerebellar atrophy (red arrow); Patient no 4 (D-F); (D) Axial T2-weighted image showing cerebellar atrophy (red arrow); (E) Axial T1-weighted image showing cerebellar atrophy (red arrow); (F) Axial FLAIR image showing cortical atrophy (red arrow).
Sea blue histiocytes in bone marrow aspirate
Figure 3
Bone marrow aspirate (A, B) showing sea blue histiocytes (red arrow).
See this image and copyright information in PMC

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