Objective: We performed a prospective analysis to determine the natural history as well as changes of electrophysiological markers in a cohort of Sialidosis type I.

Background: Sialidosis type I (ST1) is a rare autosomal recessive lysosomal storage disorder caused by mutations in the NEU1 gene. Longitudinal follow-up studies are limited.

Method: Fifteen genetically confirmed ST1 patients were recruited from multiple centers in Taiwan. All patients underwent quarterly evaluations, including Scale for the Assessment and Rating of Ataxia (SARA), and the Unified Myoclonus Rating Scale (UMRS). As well as biannual examinations including cognitive test, optical coherence tomography (OCT), fundoscopy, brain MRI and electrophysiology examinations, including evoked potentials (EP), and nerve conduction studies (NCSs).

Results: Among the 15 patients, eight carried the homozygous c.544A>G (p.Ser182Gly) mutation, while the remaining patients had compound heterozygous variants combining c.544A>G (p.Ser182Gly) with other variants. Homozygous mutation carriers have much fewer cherry-red spots or hyperreactivity on optical coherence tomography hyperreflectivity than those with compound heterozygous variants (0% vs. 100%, P<0.001). All patients have giant upper limb somatosensory EPs, prolonged lower limb F-wave latencies and delayed visual EPs. Notably, for the objective electrophysiological features, the latency of visual evoked potentials (VEP) showed significant prolongation compared with baseline in patients with compound heterozygous variants (P=0.035). In contrast, VEP latencies remained largely comparable between the two time points in homozygous carriers. Similarly, progression was also observed more prominently in the prolonged upper limb somatosensory EP latencies in compound heterozygous mutation carriers (P=0.036). In contrast, the latency remained comparable between the two time points in homozygous mutation carriers (P=0.330).

Conclusion: The NEU1 c.544A>G (p.Ser182Gly) is a common founder mutation of Taiwanese patients with ST1, patients with homozygous mutations have a later onset and slower progression of electrophysiological markers compared to those with compound heterozygous variants. These quantitative electrophysiological metrics establish viable, objective biomarkers for monitoring disease evolution and assessing future therapeutic interventions.

References: 1. Abed Rabbo M, Khodour Y, Kaguni LS, Stiban J. Sphingolipid lysosomal storage diseases: from bench to bedside. Lipids Health Dis. 2021 May 3;20(1):44. doi: 10.1186/s12944-021-01466-0. PMID: 33941173; PMCID: PMC8094529.
2. Ishibashi H, Kobayashi K, Yamanaka H, Tojima M, Oi K, Neshige S, Hitomi T, Matsuhashi M, Maruyama H, Takahashi R, Ikeda A. Redefined giant somatosensory evoked potentials: Evoked epileptic complexes of excitatory and inhibitory components. Clin Neurophysiol. 2024 Aug;164:119-129. doi: 10.1016/j.clinph.2024.05.011. Epub 2024 May 27. PMID: 38865779.
3. Hsueh SJ, Lin CH, Lee NC, Chang TM, Fan SP, Huang WD, Lin YH, Tsai LK, Chien YH, Lee MJ, Hwu WL, Hsueh HW, Yang CC. Unique clinical and electrophysiological features in the peripheral nerve system in patients with sialidosis – a case series study. Orphanet J Rare Dis. 2024 May 24;19(1):217. doi: 10.1186/s13023-024-03216-8. PMID: 38790028; PMCID: PMC11127318.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/natural-history-of-sialidosis-type-i-a-prospective-longitudinal-follow-up-study-of-clinical-and-electrophysiological-markers/