• NEU1
• ataxia
• cherry-red spots
• myoclonus
• neuraminidase 1
• sialidosis

• Humans
• Mucolipidoses/genetics
• Mucolipidoses/pathology
• Neuraminidase/genetics
• Turkey
• Male
• Female
• Mutation
• Pedigree
• Child
• Prognosis
• Adolescent
• Child, Preschool

• Alzheimer disease
• CP: Immunology
• CP: Neuroscience
• Trem2
• microglia
• neuraminidase 1
• neurodegeneration
• neuroinflammation
• sialidosis
• sialylation

• Receptors, Immunologic/metabolism
• Membrane Glycoproteins/metabolism
• Microglia/metabolism
• Microglia/pathology
• Animals
• Phagocytosis
• Neuraminidase/metabolism
• Neuraminidase/genetics
• Mice
• Signal Transduction
• Humans
• Syk Kinase/metabolism
• N-Acetylneuraminic Acid/metabolism
• Mice, Inbred C57BL

• P30 CA021765 NCI NIH HHS
• R01 GM104981 NIGMS NIH HHS
• RF1 NS123174 NINDS NIH HHS

• NEU1
• enzyme replacement therapy
• gene therapy
• genetic heterogeneity
• lysosomal storage disorder
• sialidosis

• Humans
• Neuraminidase/genetics
• Mucolipidoses/genetics
• Mucolipidoses/therapy
• Mucolipidoses/pathology
• Mutation
• Genetic Therapy
• Genetic Association Studies

• TCAS-107-02 and TCAS-112-01 Tzu Chi Medical Foundation and Tzu Chi University

• Alpha-N-acetyl neuraminidase
• Cherry-red spot
• Muscle spasm
• NEU1
• Sialidosis

• Humans
• Female
• Mucolipidoses/genetics
• Mucolipidoses/physiopathology
• Male
• Child
• Evoked Potentials, Visual/physiology
• Neuraminidase

• No. 7234365 Beijing Natural Science Foundation
• Beijing Natural Science Foundation

• Genotype
• NEU1
• Phenotype
• Sialidosis
• Structure

• 2022YFC2703600 National Key Research and Development Program of China
• 82301385 National Natural Science Foundation of China

• cardiomyopathy
• heart failure
• inflammation
• neuraminidase
• neuraminidase inhibitors

• desialylation
• sialic acids
• sialidase
• sialoglycoconjugates
• sialylation
• sialyltransferase

• NEU1 gene
• Sialidosis type 1
• electroencephalography

• desialylation
• sialic acids
• sialidase
• sialoglycoconjugates
• sialylation
• sialyltransferase

Sialidosis type 1 is a rare lysosomal storage disorder caused by mutations of the neuraminidase gene. Specific features suggesting this condition include myoclonus, ataxia and macular cherry-red spots. However, phenotypic variability exists. Here, we present detailed clinical and video description of three patients with this rare condition. We also provide an in-depth characterization of eye movement abnormalities, as an additional tool to investigate pathophysiological mechanisms and to facilitate diagnosis. In our patients, despite phenotypic differences, eye movement deficits largely localized to the cerebellum.

• eye movements
• myoclonus
• sialidosis type 1
• sodium oxybate

• animal behaviour
• glycobiology
• cognitive control
• psychiatric disorders

Type 1 sialidosis, also known as cherry-red spot-myoclonus syndrome, is a rare autosomal recessive lysosomal storage disorder presenting in the second decade of life. The most common symptoms are myoclonus, ataxia and seizure. It is rarely encountered in the Chinese mainland.

A 22-year-old male presented with complaints of progressive myoclonus, ataxia and slurred speech, without visual symptoms; the presenting symptoms began at the age of 15-year-old. Whole exome sequencing revealed two pathogenic heterozygous missense variants [c.239C>T (p.P80L) and c.544A>G (p.S182G) in the neuraminidase 1 (NEU1) gene], both of which have been identified previously in Asian patients with type 1 sialidosis. All three patients identified in Mainland China come from three unrelated families, but all three show the NEU1 mutations p.S182G and p.P80L pathogenic variants. Increasing sialidase activity through chaperones is a promising therapeutic target in sialidosis.

Through retrospective analysis and summarizing the clinical and genetic characteristics of type 1 sialidosis, we hope to raise awareness of lysosomal storage disorders among clinicians and minimize the delay in diagnosis.

• Sialidosis
• Myoclonus
• Ataxia
• Neuraminidase 1
• Case report
• Mucolipidoses

• genetics, myoclonus, ataxia, movement disorders, diagnosis

• Ataxia
• Cherry red spot
• Mild mutation
• Myoclonus
• Sialidosis type I

Background: Sialidosis is a rare autosomal recessive disease caused by NEU1 mutations, leading to neuraminidase deficiency and accumulation of sialic acid-containing oligosaccharides and glycopeptides into the tissues. Sialidosis is divided into two clinical entities, depending on residual enzyme activity, and can be distinguished according to age of onset, clinical features, and progression. Type 1 sialidosis is the milder, late-onset form, also known as non-dysmorphic sialidosis. It is commonly characterized by progressive myoclonus, ataxia, and a macular cherry-red spot. As a rare condition, the diagnosis is often only made after few years from onset, and the clinical management might prove difficult. Furthermore, the information in the literature on the long-term course is scarce. Case presentations: We describe a comprehensive clinical, neuroradiological, ophthalmological, and electrophysiological history of four unrelated patients affected by type 1 sialidosis. The long-term care and novel clinical and neuroradiological insights are discussed. Discussion and conclusions: We report the longest follow-up (up to 30 years) ever described in patients with type 1 sialidosis. During the course, we observed a high degree of motor and speech disability with preserved cognitive functions. Among the newest antiseizure medication, perampanel (PER) was proven to be effective in controlling myoclonus and tonic–clonic seizures, confirming it is a valid therapeutic option for these patients. Brain magnetic resonance imaging (MRI) disclosed new findings, including bilateral gliosis of cerebellar folia and of the occipital white matter. In addition, a newly reported variant (c.914G > A) is described.

• brain MRI
• cherry-red spot
• giant SEP
• jerk-locked back averaging analysis
• myoclonus
• type-1-sialidosis

Type I sialidosis (ST‐1) is a rare autosomal recessive inherited disorder. To date, there has been no study on ST‐1 patients in mainland China.

We reported in detail the cases of five Chinese ST‐1 patients from two centers, and summarized all worldwide cases. Then, we compared the differences between Chinese and foreign patients.

A total of 77 genetically confirmed ST‐1 patients were identified: 12 from mainland China, 23 from Taiwan, 10 from other Asian regions, and 32 from European and American regions. The mean age of onset was 16.0 ± 6.7 years; the most common symptoms were myoclonus seizures (96.0%), followed by ataxia (94.3%), and blurred vision (67.2%). Compared to other groups, the onset age of patients from mainland China was much younger (10.8 ± 2.7 years). The incidence of visual impairment was lower in patients from other Asian regions than in patients from mainland China and Taiwan (28.6% vs. 81.8%–100%). Cherry‐red spots were less frequent in the Taiwanese patients than in patients from other regions (27.3% vs. 55.2%–90.0%). Furthermore, 48 different mutation types were identified. Chinese mainland and Taiwanese patients were more likely to carry the c.544A > G mutation (75% and 100%, respectively) than the patients from other regions (only 0%–10.0%). Approximately 50% of Chinese mainland patients carried the c.239C > T mutation, a much higher proportion than that found in the other populations. In addition, although the brain MRI of most patients was normal, ¹⁸F‐FDG‐PET analysis could reveal cerebellar and occipital lobe hypometabolism.

ST‐1 patients in different regions are likely to have different mutation types; environmental factors may influence clinical manifestations. Larger studies enrolling more patients are required.

Sialidosis type 1 is a rare inherited disorder with a high disability. No genetically confirmed mainland Chinese patient with sialidosis type 1 has been reported. This study evaluated the phenotypes and genotypes of mainland Chinese patients with sialidosis type 1.

It was a retrospective case series study. Four unrelated patients were enrolled. Comprehensive clinical evaluations and molecular genetic analysis of the NEU1 gene were performed.

Three out of four patients presented progressive myoclonus epilepsy. The best‐corrected visual acuity ranged from 20/2000 to 20/25. Punctate cataracts were found in all of the patients. Distinct macular cherry red spots were observed in three patients by fundoscopy, and a relatively normal fundus was revealed in one patient. Optical coherence tomography (OCT) showed increased reflectivity of the nerve fiber and ganglion cell layers, and fundus autofluorescence (FAF) revealed hyperautofluorescent areas surrounding the fovea in all of the patients. Only superficial retinal vessels can be observed using OCT angiography; the deeper capillary plexus could not be observed. Visual evoked potential revealed varying degrees of decreased amplitude and/or prolonged latency of P100 or P2 waves. The most frequent sequence variant identified was c.544A>G (p.S182G) (NM_000434.3).

Our study first described the ophthalmic and neurologic characteristics of a small cohort of unrelated mainland Chinese patients with sialidosis type 1. We found that c.544A>G (p. S182G) might be a hotspot variant in Chinese patients. The accumulation of metabolic products in the nerve fiber and ganglion cell layers is a characteristic ocular finding that could be sensitively detected by OCT and FAF imaging.

• FAF
• OCT
• OCTA
• macular cherry red spot
• sialidosis type 1

• neu1
• Large genomic deletion
• cherry-red
• pseudo-homozygous mutation
• spot
• whole genome sequencing

• Ataxia
• Evoked potential
• Myoclonus
• NEU1
• Sialidosis