Clinical, ocular motor, and imaging profile of Niemann-Pick type C heterozygosity.

Bremova-Ertl, Tatiana; Sztatecsny, Clara; Brendel, Matthias; Moser, Marlene; Möller, Bettina; Clevert, Dirk A; Beck-Wödl, Stefanie; Kun-Rodrigues, Celia; Bras, Jose; Rominger, Axel; Ninov, Dimitar; Strupp, Michael; Schneider, Susanne A (2020). Clinical, ocular motor, and imaging profile of Niemann-Pick type C heterozygosity. Neurology, 94(16), e1702-e1715. American Academy of Neurology 10.1212/WNL.0000000000009290

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To characterize subclinical abnormalities in asymptomatic heterozygote NPC1 mutation carriers as markers of neurodegeneration.


Motor function, cognition, mood, sleep, and smell function were assessed in 20 first-degree heterozygous relatives of patients with Niemann-Pick disease type C (NPC) (13 male, age 52.7 ± 9.9 years). Video-oculography and abdominal ultrasound with volumetry were performed to assess oculomotor function and size of liver and spleen. NPC biomarkers in blood were analyzed. 18F-fluorodesoxyglucose PET was performed (n = 16) to detect patterns of brain hypometabolism.


NPC heterozygotes recapitulated characteristic features of symptomatic NPC disease and demonstrated the oculomotor abnormalities typical of NPC. Hepatosplenomegaly (71%) and increased cholestantriol (33%) and plasma chitotriosidase (17%) levels were present. The patients also showed signs seen in other neurodegenerative diseases, including hyposmia (20%) or pathologic screening for REM sleep behavior disorder (24%). Cognitive function was frequently impaired, especially affecting visuoconstructive function, verbal fluency, and executive function. PET imaging revealed significantly decreased glucose metabolic rates in 50% of participants, affecting cerebellar, anterior cingulate, parieto-occipital, and temporal regions, including 1 with bilateral abnormalities.


NPC heterozygosity, which has a carrier frequency of 1:200 in the general population, is associated with abnormal brain metabolism and functional consequences. Clinically silent heterozygous gene variations in NPC1 may be a risk factor for late-onset neurodegeneration, similar to the concept of heterozygous GBA mutations underlying Parkinson disease.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Brémovà-Ertl, Tatiana and Rominger, Axel Oliver


600 Technology > 610 Medicine & health




American Academy of Neurology




Chantal Kottler

Date Deposited:

15 Jul 2020 10:20

Last Modified:

07 Dec 2020 11:49

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