Niemann Pick Type C

Vertical supranuclear gaze palsy as key feature

Niemann-Pick type C (NPC) is an autosomal recessive lysosomal storage disorder caused by mutations in either the NPC1 or the NPC2 gene^{1, 2}. Vertical supranuclear gaze palsy is a key feature of NPC and is present in approximately 65% of patients^{1, 2, 3}.

In particular, downward saccades are affected first (controlled unilaterally) followed by upward saccades (controlled bilaterally). Horizontal saccades are initially preserved, but are also affected as the disease progresses³. A so-called round-the-houses phenomenon occurs when attempting vertical saccades: the eyes do not move directly up and down, but in a lateral arc³. 

Supranuclear gaze palsy carries high clinical significance for the diagnosis of NPC as it occurs early in the disease and can lead to disease-specific treatment^{1, 2, 4}. In fact, vertical saccade paresis may be present even before the internal, neurological or psychiatric manifestations and sometimes is the only symptom of NPC in adults and indicates a “red flag”, signalling that further examinations are needed⁵. 

In a video-based eye tracking study mentioned in the review by Crotty at at⁴, abnormal curvature and slowed downward gaze have been found in both children with neurological NPC and presymptomatic NPC, but not in healthy controls⁶. This early identification of abnormal eye tracking in presymptomatic cases suggests it could be a sensitive tool for early detection of NPC⁴.

The early identification of NPC and the appropriate use of symptomatic and disease-specific therapies can dramatically improve the quality of life of these patients¹.

1. Strupp M, Kremmyda O, Adamczyk C, et al. Central ocular motor disorders, including gaze palsy and nystagmus. J Neurol. 2014;261(S2):542-558. doi:10.1007/s00415-014-7385-9
   
   

2. Kassavetis P, Kaski D, Anderson T, Hallett M. Eye Movement Disorders in Movement Disorders. Mov Disord Clin Pract. 2022;9(3):284-295. doi:10.1002/mdc3.13413

3. Koens LH, Tuitert I, Blokzijl H, et al. Eye movement disorders in inborn errors of metabolism: A quantitative analysis of 37 patients. J Inherit Metab Dis. Published online July 11, 2022:jimd.12533. doi:10.1002/jimd.12533

4. Crotty GF, Chwalisz BK. Ocular motor manifestations of movement disorders. Curr Opin Ophthalmol. 2019;30(6):443-448. doi:10.1097/ICU.0000000000000605

5. Lowenstein O. Clinical pupillary symptoms in lesions of the optic nerve, optic chiasm, and optic tract. AMA Arch Ophthalmol. 1954;52(3):385-403. doi:10.1001/archopht.1954.00920050387006

6. Bares M, Brázdil M, Kanovský P, et al. The effect of apomorphine administration on smooth pursuit ocular movements in early Parkinsonian patients. Parkinsonism Relat Disord. 2003;9(3):139-144. doi:10.1016/s1353-8020(02)00015-9