Gaucher Disease

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the gene GBA1, which encodes the lysosomal protein glucocerebrosidase, leading to accumulation of this protein in the tissue macrophages, which affects the hematological, visceral, bone, and neurologic systems^1,2–4. 

Patients with GD generally have a variety of clinical manifestations, including visceral, neurological and ocular. This disorder is classified into three types: type 1 (non-neuronopathic), type 2 (acute neuronopathic) and type 3 (chronic neurological manifestations)^1,3. 

Type 2 GD presents during infancy and abnormalities of eye movements are early signs in affected children, including ocular motor paralysis, slowness of saccades, oculomotor “apraxia,” and strabismus.⁴

Type 3 GD presents during childhood or adolescence. Many patients with type 3 GD present with or develop neuro-ophthalmologic findings⁵. The hallmark clinical abnormality in type 3 GD consists of slow horizontal saccades, which leads progressively to horizontal eye supranuclear palsy, and has been used to differentiate type 3 GD from other types of GD^{1, 2, 3}.

Studies have found a correlation between the severity of neurological impairment in type 3 GD and the latency of horizontal saccades and antisaccades⁵. Involvement of the vertical saccade is less commonly encountered in type 3 GD². Downward saccades are more affected than upward saccades and correlate with neurological impairment². These saccadic abnormalities are important parameters for diagnosis and follow-up of GD patients^{2, 4}. 

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. Eghbali A, Hassan S, Seehra G, FitzGibbon E, Sidransky E. Ophthalmological findings in Gaucher disease. Mol Genet Metab. 2019;127(1):23-27. doi:10.1016/j.ymgme.2019.02.002

3. Roshan Lal T, Sidransky E. The Spectrum of Neurological Manifestations Associated with Gaucher Disease. Dis Basel Switz. 2017;5(1):10. doi:10.3390/diseases5010010

4. 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.1253

5. Thurtell MJ, Leigh RJ. Nystagmus and saccadic intrusions. In: Handbook of Clinical Neurology. Vol 102. Elsevier; 2011:333-378. doi:10.1016/B978-0-444-52903-9.00019-4