Sialidosis type I (ST-1) is an autosomal-recessive, very rare, progressive lysosomal storage disorder caused by pathogenic variants in NEU1. It is clinically characterized by progressive ataxia, myoclonic seizures (MS), bilateral tonic-clonic seizures (BTCS), and distinctive ophthalmological findings. Given the lack of curative options, in this study, we investigated symptomatic treatment strategies, with a particular focus on the efficacy of antiseizure medications (ASMs). We describe the clinical course of a patient followed from diagnosis to 18 years of age, and review seven additional cases from our cohort. In parallel, we conducted a narrative review of the literature (PubMed, January 2010-September 2025) to identify published reports containing therapeutic data. Therapeutic responses were evaluated in a total of 33 cases (8 from our cohort, 25 from published sources). Although available data are insufficient to define standardized treatment guidelines, some ASMs, such as ACZ, PER, LEV, VPA, CZP, and ZNS, demonstrated fairly consistent efficacy in managing MS and BTCS. Sodium oxybate or deep-brain stimulation may be considered in refractory cases. Prospective documentation of clinical course and treatment outcomes-ideally through an international registry-is crucial to improve patient care and inform therapeutic strategies. Sialidosis type I (ST-1) is a very rare genetic disorder causing movement problems and seizures, with no cure available yet. We followed 8 patients and reviewed 25 published cases to assess treatments focusing on myoclonic seizure (MS) control. Some antiseizure medications showed benefit. However, we have too little data to make clear recommendations. To improve patients' treatment and to choose the most appropriate therapy, it would be important to follow patients over a longer period of time, for example, in an international registry.

Sialidosis type 1 is a rare autosomal recessive lysosomal storage disorder caused by pathogenic variants in the NEU1 gene, which encodes the sialic acid-degrading enzyme α-neuraminidase. Sialidosis type 1 is a milder form with a late-onset phenotype, characterized by progressive myoclonic epilepsy and ataxia with cherry-red spots. Sialidosis type 2 is an early-onset and more severe form presenting with dysmorphic features, hepatosplenomegaly and cognitive delay. Clinical diagnosis is usually supported by increased urinary bound sialic acid excretion and confirmed by genetic analysis or demonstration of α-neuraminidase enzyme deficiency in cultured fibroblasts. The aim of this study was to present a case of type 1 sialidosis, review the literature, and investigate genotype-phenotype correlations, symptom frequencies, and race-specific mutations in patients diagnosed with type 1 sialidosis. We report herein a family of four Turkish siblings affected with sialidosis type 1 associated with a homozygous variant, c.403G>A p. (Asp135Asn), in the NEU1 gene. A systematic literature review on sialidosis type 1 was carried out, by the PubMed database was searched using keywords included sialidosis and/or NEU1 gene. We selected case reports or series that included genetically confirmed type 1 sialidosis from 1996 to 2023. So far, nearly genetically confirmed 80 patients from unrelated 65 families, more than 40 NEU1 disease causing mutations, have been identified in patients with sialidosis type 1. Among the reported mutations, missense variants are the most common, and few nonsense, frameshift, exonic duplications or small deletions have been reported. c.239C>T p. (Pro80Leu) variant in Chinese and Japanese patients, c.649G>A p. (Val217Met) variant in Japanese patients, c.880C>T p. (Arg294Cys) variant in Indian patients, c.629C>T p. (Pro210Leu) variant in Ecuadorian patients, c.982G>A p. (Gly328Ser) variant in Italian patients, and c.403G>A p (Asp135Asn) and c.625del p. (Glu209Serfs*94) variants in Turkish patients were found higher. Race-specific variants were found with higher percentages in certain populations.

Sialidosis type 1 (ST-1) is a rare autosomal recessive disorder caused by mutation in the NEU1 gene. However, limited reports on ST-1 patients in the Chinese mainland are available. This study reported the genetic and clinical characteristics of 10 ST-1 patients from southeastern China. A haplotype analysis was performed using 21 single nucleotide polymorphism (SNP) markers of 500 kb flanking the recurrent c.544 A > G in 8 families harboring the mutation. Furthermore, this study summarized and compared previously reported ST-1 patients from Taiwan and mainland China. Five mutations within NEU1 were found, including two novel ones c.557 A > G and c.799 C > T. The c.544 A > G mutation was most frequent and identified in 9 patients, 6 patients were homozygous for c.544 A > G. Haplotype analysis revealed a shared haplotype surrounding c.544 A > G was identified, suggesting a founder effect presenting in southeast Chinese population. Through detailed assessment, 52 ST-1 patients from 45 families from Taiwan and mainland China were included. Homozygous c.544 A > G was the most common genotype and found in 42.2% of the families, followed by the c.544 A > G/c.239 C > T compound genotype, which was observed in 22.2% of the families. ST-1 patients with the homozygous c.544 A > G mutation developed the disease at a later age and had a lower incidence of cherry-red spots significantly. The results contribute to gaps in the clinical and genetic features of ST-1 patients in southeastern mainland China and provide a deeper understanding of this disease to reduce misdiagnosis.

Sialidosis is a rare disorder caused by mutations in the NEU1 gene located on chromosome 6p21.3, constituting a group of autosomal recessive diseases. Enzyme activity analysis, electron microscopy examination and genetic testing are reliable methods for diagnosis. Despite previous reports on the disease, its rarity means that its clinical manifestations and prognosis still warrant attention due to the limited amount of information available. We report a case of a 40-year-old woman who was admitted to our hospital for worsening dysarthria of 16 years duration and facial and limb twitching that had been present for 2 years. Genetic testing was undertaken. Genetic testing confirmed type I sialidosis, the first reported instance of this disease in the Hainan Free Trade Port in China. The patient did not have the typical cherry-red spot in the fundus. Despite aggressive treatment, she died of status epilepticus 2 months later. This result indicates that the disease has a poor prognosis. Cherry-red spots in the fundus are characteristic features of type I sialidosis and it has been referred to as the cherry-red spot myoclonus syndrome. We hypothesise that environmental factors may also play a significant role. Overemphasis on the presence of cherry-red spots may mislead clinicians and delay diagnosis. Furthermore, patients presenting with isolated myoclonus should undergo visual evoked potential and somatosensory evoked potential tests, as well as genetic testing to confirm or rule out sialidosis.

Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying N-acetyl-α-neuraminidase-1 (NEU1) variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1. First, whole-exome sequencing and detailed clinical examinations were performed on the family. Second, structural analyses, including assessments of energy, flexibility and polar contacts, were conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed. We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by a sialidase activity assay. Cherry-red spots were more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal electroencephalographies and visual evoked potentials had a relatively early age of onset, whereas patients with myoclonus had a late onset. Changes in flexibility and local polar contacts may be indicators of NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.