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.

REFERENCES

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

Interested? Read more!

The American Academy of Ophthalmology maintains an EyeWiki written by physicians and surgeons.

Read their literature review regarding Vertical Gaze Palsy here.

Ocular motor study in patients with Niemann Pick disease Type C

Eye movement abnormalities are sensitive markers in neurodegenerative disorders. One such rare autosomal recessive inborn error of metabolism is Niemann-Pick disease type C (NPC), caused by a mutation in the NPC1 (95%) or NPC2 genes.

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

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 heterozygotes recapitulated characteristic features of symptomatic NPC disease and demonstrated the oculomotor abnormalities typical of NPC.