Clinical and electrophysiological characteristics of a type 1 sialidosis patient with a novel deletion mutation in NEU1 gene

Background/purpose: Type 1 sialidosis is a rare autosomal recessive lysosomal storage disease caused by Neuraminidase 1 (NEU1) gene mutations. We report a type 1 sialidosis patient with a novel deletion mutation in NEU1 and compared the phenotypes within different ethnicities. Methods: Targeted next generation sequencing and segregation analysis were performed to identify the causative gene mutation of the index patient. The clinical and electrophysiological characteristics of the patient were compared to those reported in previous studies of type 1 sialidosis from 1996 to 2019. Results: A 16-year-old boy presented with progressive onset of seizure, myoclonus, and ataxia since 5 years of age. Targeted next generation sequencing revealed the pathogenic missense variant c.544A>G (p.Ser182Gly) and the novel c.314_352del (p.A106_G118del) deletion in NEU1 in a compound heterozygote state. The leukocyte neuraminidase activity was significantly decreased (0.0323 nmol/mg protein/hour, normal reference: 0.326 +/- 0.095 nmol/mg protein/hour). A total of 46 patients were identified in 18 reports from the literature. The most common symptoms were myoclonus (100%), followed by ataxia (88.3%) and seizure (72.5%). Notably, impaired cognition (50.0% vs. 21.7%, P = 0.04) and cherry-red spots (61.1% vs. 40.7%, P = 0.02) were less frequently reported in Asian patients than in Caucasian patients. Abnormal somatosensory evoked potentials with giant cortical waves and prolonged visual evoked potential latency were found consistently in Asian and Caucasian patients, and could be a surrogate marker of early diagnosis. Conclusion: Our findings suggest a distinct phenotype of infrequent cherry-red spots and abnormal evoked potentials in Asian patients with type 1 sialidosis. Copyright (C) 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC.