Abstract
ObjectiveNiemann–Pick disease type C1 (NPC1) is a rare autosomal-recessive lysosomal storage disorder presenting with a broad clinical spectrum ranging from a severe infantile-onset neurovisceral disorder to late-onset neurodegenerative disease. Optical coherence tomography (OCT) is established to detect retinal degeneration in vivo. We examined NPC1-patients (NPC1-P), clinically asymptomatic NPC1-mutation carriers (NPC1-MC), and healthy controls (HC) to (1) identify retinal degeneration in NPC1-disease and (2) to investigate possible subclinical retinal degeneration in NPC1-MC.MethodsFourteen NPC1-P, 17 NPC1-MC, and 31 age-matched HC were examined using spectral-domain OCT. Neurological examinations, clinical scales [modified Disability Rating Scale (mDRS); Scale for the Rating and Assessment of Ataxia (SARA); Spinocerebellar Ataxia Functional Index (SCAFI)], and video-oculography (VOG) were correlated with OCT data.ResultsMacular retinal nerve fiber layer and volumes of combined ganglion cell and inner plexiform layer were significantly lower in NPC1-P compared to HC [mRNFL (µm):0.13 ± 0.01 vs. 0.14 ± 0.02; p = 0.01; GCIPL (mm3):0.60 ± 0.05 vs. 0.62 ± 0.04; p = 0.04]. No significant differences were found in NPC1-MC in comparison to HC. In NPC1-P, the amplitude of upward vertical saccades showed positive associations with peripapillary RNFL (ρ = 0.645; p < 0.05), and thinned GCIP (ρ = 0.609; p < 0.05), but not in NPC1-MC. In NPC1-P correlations between combined outer plexiform layer and outer nuclear layer (OPONL) with mDRS (r = − 0.617; p < 0.05) and GCIP with SARA (r = − 0.622; p < 0.05) were observed. Furthermore, in NPC1-MC, motor scores were negatively associated with pRNFL (ρ = − 0.677; p < 0.01).ConclusionsUsing OCT, we showed retinal degeneration in NPC1-P and significant correlation between retinal neuroaxonal degeneration with clinical measurements. We observed a non-significant trend of retinal degeneration in NPC1-MC correlating with subclinical motor abnormalities. Based on these preliminary data, OCT may be an important marker of neurodegeneration in NPC1-disease after onset of clinical symptoms.
Highlights
Niemann–Pick disease type C (NPC) is an autosomal recessively inherited neurovisceral lysosomal disorder caused by mutations in the Niemann–Pick disease type C1 (NPC1) or NPC2 gene [1, 2]
We examined NPC1-P, clinically healthy NPC1-MC, and healthy controls (HC) using Optical coherence tomography (OCT) to (i) identify retinal degeneration in NPC disease using a non-invasive OCT technique and (ii) to investigate for possible subclinical retinal atrophy in NPC1-mutation carriers (MC)
We evaluated 26 eyes of 14 NPC1-P and 34 eyes of 17 NPC1-MC
Summary
Niemann–Pick disease type C (NPC) is an autosomal recessively inherited neurovisceral lysosomal disorder caused by mutations in the NPC1 or NPC2 gene [1, 2]. The clinical phenotype ranges from an infancy-onset progressive, fatal. Extended author information available on the last page of the article disorder to an adult-onset, chronic neurodegenerative disease with heterogeneous clinical symptoms such as cognitive impairment, cerebellar symptoms, dystonia, vertical supranuclear saccade and gaze palsy, psychiatric disorders, and, less frequently, epilepsy [3]. Markers reflecting disease progression in NPC are not well established. NPC is characterized by abnormalities of intracellular transport of endocytosed cholesterol and further lipids with their sequestration in lysosomes and late endosomes [5, 6]. Dysregulation of brain cholesterol homeostasis is present in some of the common neurodegenerative central nerve system (CNS) disorders
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