RARE DISEASE
Sialidosis
Sialidosis
Sialidosis
Drug discovery
0
drugs
With orphan designations
Overview
Sialidosis is a rare autosomal recessive lysosomal storage disorder caused by NEU1 gene mutations, resulting in neuraminidase deficiency and accumulation of sialylated metabolites. It manifests as type I (late-onset, normosomatic) with myoclonus, ataxia, vision loss, and cherry-red spots, or type II (early-onset, dysmorphic) with developmental delay, organomegaly, dysostosis multiplex, and neonatal lethality in severe forms. Diagnosis relies on genetic testing and enzyme assays. Management is supportive, focusing on symptom control [1][6][13].
Burden
Type I: Progressive motor disability (wheelchair dependency) and vision impairment with preserved cognition [7][13].
Type II: High mortality (neonatal hydrops, organ failure); multisystem complications increase healthcare costs [6][10][13].
No disease-modifying treatments; lifelong multidisciplinary care required [1][8].
Categories: rare genetic diseases, rare inborn errors of metabolism, rare ophthalmic disorders
Research Papers
81 drug discovery papers about Sialidosis, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
81 drug discovery papers about Sialidosis, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-04-01 | Lysosomal Neuraminidase 1 (NEU1): Its Unique Molecular Characters and Therapeutic Approaches for Deficiencies.
Neuraminidase 1 (NEU1) is a lysosomal sialidase that removes terminal α-bound sialic acid from sialylglycoconjugates and contributes to ubiquitous catabolism of sialylglycoconjugates and immunoregulatory functions. Different from other human sialidases, including NEU2 to NEU4, NEU1 is first produced as an N-glycosylated precursor protein, which binds to its protective protein/cathepsin A (CTSA) and then forms a lysosomal multienzyme complex (LMC) with β-galactosidase 1 (GLB1) in the rough endoplasmic reticulum (RER) lumen. NEU1 trafficking to lysosomes and intralysosomal activation under acidic pH conditions essentially requires association with CTSA, which carries terminal mannose 6-phosphate (M6P)-type N-glycan to bind with cation-dependent (CD) M6P receptor (CD-M6PR) in the Golgi apparatus via endosomes. In contrast, the single NEU1 gene overexpression in mammalian cells results in NEU1 protein crystallization in the RER owing to self-aggregation at a relatively low intrinsic CTSA level. Two NEU1 deficiencies, sialidosis (SiD) and galactosialidosis (GS), are caused by autosomal recessive NEU1 and CTSA gene mutations, respectively. These untreatable disorders are associated with excessive storage of sialylglycans in neurovisceral organs and systemic symptoms. We produced a new GS model mouse by introducing a homozygous Ctsa IVS6+1g/a mutation into the murine gene locus, leading to partial exon 6 skipping and simultaneous deficiency of Ctsa and Neu1. The GS mice exhibited clinical symptoms similar to those seen in juvenile/adult GS patients, including myoclonic seizures, suppressed behavior, a gargoyle-like face, edema, proctoptosis owing to Neu1 deficiency, and sialylglycan accumulation related to neurovisceral inflammation. Evaluating the efficacy of a novel therapy utilizing GS and SiD model mice and overcoming the human NEU1 gene product shortage will be necessary for a novel, effective treatment for NEU1 deficiencies.
2026-02-10 | Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature.
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.
2026-02-10 | Alterations in secondary lipids are associated with neuroinflammation in the brain of Neu1-deficient mice.
Neu1 (lysosomal sialidase 1) is essential for removing sialic acid from oligosaccharides and glycoconjugates. Neu1 deficiency impairs lysosomal digestion, leading to sialidosis and sialoglycoprotein accumulation. It also increases lipids, including gangliosides GM3, GD3, GM4, and LM1, in the kidney, liver, and spleen. Neu1-/- mice display symptoms resembling Type II sialidosis, including enlarged spleen and liver, kidney issues, neurological problems, spinal defects, and oligosaccharide buildup. The study examined secondary lipid alterations and inflammation in the cortex and cerebellum of these mice. Lipidomic, molecular, and immunohistochemical analyses of tissues from 2 and 5 M Neu1-/- mice revealed reduced levels of lipids, including PC, PE, PS, and CL, along with increased pro-inflammatory cytokines and loss of oligodendrocytes and neurons. Signs of astrogliosis and microgliosis emerged in specific brain regions. These results indicate that reduced levels of glycerophospholipids could serve as an indicator of inflammation in sialidosis mice. Future research should investigate therapies targeting these lipid changes, as modulating glycerophospholipids might slow disease progression in sialidosis patients.
2026-01-06 | Failure of Allogeneic Transplant to Correct Sialidosis Despite Early Diagnosis and Full Donor Engraftment of Non-Carrier Leucocytes.
Sialidosis, also known as Mucolipidosis Type I, is a rare condition caused by defects in the NEU1 gene which causes the accumulation of sialylated peptides, oligosaccharides, and glycoproteins leading to neurological decline. Haematopoetic stem cell transplantation has been performed in the symptomatic phase twice in the literature but has failed to prevent deterioration. We report on a case where a 4-year-old child was diagnosed with pre-symptomatic sialidosis due to investigation following the incidental detection of a cherry-red spot prior to the onset of neurological symptoms. We performed haematopoetic stem cell transplantation with a matched unrelated cord blood unit with optimal timing prior to clinical decline, achieving full donor engraftment with a largely uneventful post-transplant recovery followed by a period of relative clinical stability. However, subsequent neurological decline detailed by clinical history and radiological findings has occurred suggesting a lack of disease responsiveness to transplantation despite optimal timing. We go on to provide supporting laboratory investigations detailing sialidosis fibroblast culture as part of a novel cross-correction assay and compare results to other transplant responsive lysosomal storage disorders such as mucopolysaccharidosis type 1-H and detail a lack of cross-correction in concordance with our clinical findings. We conclude that conventional allogeneic haematopoetic stem cell transplantation is not a viable disease-modifying treatment option in sialidosis, even when performed optimally in the pre-symptomatic phase, and suggest that alternative treatment options must be explored to improve outcomes in this condition.
2025-07-17 | Sialidosis type1 with cardiac malformation: A case report
Sialidosis is a rare autosomal recessive lysosomal storage disease caused by a variant in the neuraminidase 1 (NEU1) gene encoding lysosomal neuraminidase, and is a rare cause of progressive myoclonus epilepsies (PME). Sialidosis is classified into two types. Sialidosis type 1 is a relatively mild late-onset form with ataxia, myoclonus, macular cherry-red spot, seizures, and non-dysmorphic features. Sialidosis type 2 has congenital, infantile and juvenile-onset forms, and has more severe feature, including ascites, coarse facies, dysostosis multiplex, macular cherry-red spot, hepatosplenomegaly, and developmental delay than type 1. Our case, a 29-year-old male, had shown normal development up to the age of 12 years and 5 months. Subsequently, he developed ataxia and myoclonus. At age 12 years and 11 months, generalized tonic-clonic seizures occurred with ataxia, myoclonus, intentional tremor, borderline intelligence, and cherry-red macular spot. Skin fibroblast enzymological analysis of neuraminidase yielded a value below 1 nmol/h/mg protein. NEU1 gene findings were consistent with compound heterozygous missense variant c.1034C>T(p.Thr345Ile) and c.239C>T(p.Pro80Leu), while electron microscopy of skinfibroblasts showed vacuoles and dense body deposition in both neuroblasts and Schwann cells. In addition, this is the first reported case of sialidosis type 1 associated with a quadricuspid aortic valve malformation. Collectively, the above findings indicated a diagnosis of sialidosis type 1 with cardiac malformation. The involuntary movement improved temporarily in response to clonazepam but then gradually worsened. During 17 years of follow-up, his seizures were controlled with anticonvulsants, but the ataxia, myoclonus and intentional tremor gradually worsened.
2026-04-01 | Lysosomal Neuraminidase 1 (NEU1): Its Unique Molecular Characters and Therapeutic Approaches for Deficiencies.
Neuraminidase 1 (NEU1) is a lysosomal sialidase that removes terminal α-bound sialic acid from sialylglycoconjugates and contributes to ubiquitous catabolism of sialylglycoconjugates and immunoregulatory functions. Different from other human sialidases, including NEU2 to NEU4, NEU1 is first produced as an N-glycosylated precursor protein, which binds to its protective protein/cathepsin A (CTSA) and then forms a lysosomal multienzyme complex (LMC) with β-galactosidase 1 (GLB1) in the rough endoplasmic reticulum (RER) lumen. NEU1 trafficking to lysosomes and intralysosomal activation under acidic pH conditions essentially requires association with CTSA, which carries terminal mannose 6-phosphate (M6P)-type N-glycan to bind with cation-dependent (CD) M6P receptor (CD-M6PR) in the Golgi apparatus via endosomes. In contrast, the single NEU1 gene overexpression in mammalian cells results in NEU1 protein crystallization in the RER owing to self-aggregation at a relatively low intrinsic CTSA level. Two NEU1 deficiencies, sialidosis (SiD) and galactosialidosis (GS), are caused by autosomal recessive NEU1 and CTSA gene mutations, respectively. These untreatable disorders are associated with excessive storage of sialylglycans in neurovisceral organs and systemic symptoms. We produced a new GS model mouse by introducing a homozygous Ctsa IVS6+1g/a mutation into the murine gene locus, leading to partial exon 6 skipping and simultaneous deficiency of Ctsa and Neu1. The GS mice exhibited clinical symptoms similar to those seen in juvenile/adult GS patients, including myoclonic seizures, suppressed behavior, a gargoyle-like face, edema, proctoptosis owing to Neu1 deficiency, and sialylglycan accumulation related to neurovisceral inflammation. Evaluating the efficacy of a novel therapy utilizing GS and SiD model mice and overcoming the human NEU1 gene product shortage will be necessary for a novel, effective treatment for NEU1 deficiencies.
2026-02-10 | Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature.
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.
2026-02-10 | Alterations in secondary lipids are associated with neuroinflammation in the brain of Neu1-deficient mice.
Neu1 (lysosomal sialidase 1) is essential for removing sialic acid from oligosaccharides and glycoconjugates. Neu1 deficiency impairs lysosomal digestion, leading to sialidosis and sialoglycoprotein accumulation. It also increases lipids, including gangliosides GM3, GD3, GM4, and LM1, in the kidney, liver, and spleen. Neu1-/- mice display symptoms resembling Type II sialidosis, including enlarged spleen and liver, kidney issues, neurological problems, spinal defects, and oligosaccharide buildup. The study examined secondary lipid alterations and inflammation in the cortex and cerebellum of these mice. Lipidomic, molecular, and immunohistochemical analyses of tissues from 2 and 5 M Neu1-/- mice revealed reduced levels of lipids, including PC, PE, PS, and CL, along with increased pro-inflammatory cytokines and loss of oligodendrocytes and neurons. Signs of astrogliosis and microgliosis emerged in specific brain regions. These results indicate that reduced levels of glycerophospholipids could serve as an indicator of inflammation in sialidosis mice. Future research should investigate therapies targeting these lipid changes, as modulating glycerophospholipids might slow disease progression in sialidosis patients.
2026-01-06 | Failure of Allogeneic Transplant to Correct Sialidosis Despite Early Diagnosis and Full Donor Engraftment of Non-Carrier Leucocytes.
Sialidosis, also known as Mucolipidosis Type I, is a rare condition caused by defects in the NEU1 gene which causes the accumulation of sialylated peptides, oligosaccharides, and glycoproteins leading to neurological decline. Haematopoetic stem cell transplantation has been performed in the symptomatic phase twice in the literature but has failed to prevent deterioration. We report on a case where a 4-year-old child was diagnosed with pre-symptomatic sialidosis due to investigation following the incidental detection of a cherry-red spot prior to the onset of neurological symptoms. We performed haematopoetic stem cell transplantation with a matched unrelated cord blood unit with optimal timing prior to clinical decline, achieving full donor engraftment with a largely uneventful post-transplant recovery followed by a period of relative clinical stability. However, subsequent neurological decline detailed by clinical history and radiological findings has occurred suggesting a lack of disease responsiveness to transplantation despite optimal timing. We go on to provide supporting laboratory investigations detailing sialidosis fibroblast culture as part of a novel cross-correction assay and compare results to other transplant responsive lysosomal storage disorders such as mucopolysaccharidosis type 1-H and detail a lack of cross-correction in concordance with our clinical findings. We conclude that conventional allogeneic haematopoetic stem cell transplantation is not a viable disease-modifying treatment option in sialidosis, even when performed optimally in the pre-symptomatic phase, and suggest that alternative treatment options must be explored to improve outcomes in this condition.
2025-07-17 | Sialidosis type1 with cardiac malformation: A case report
Sialidosis is a rare autosomal recessive lysosomal storage disease caused by a variant in the neuraminidase 1 (NEU1) gene encoding lysosomal neuraminidase, and is a rare cause of progressive myoclonus epilepsies (PME). Sialidosis is classified into two types. Sialidosis type 1 is a relatively mild late-onset form with ataxia, myoclonus, macular cherry-red spot, seizures, and non-dysmorphic features. Sialidosis type 2 has congenital, infantile and juvenile-onset forms, and has more severe feature, including ascites, coarse facies, dysostosis multiplex, macular cherry-red spot, hepatosplenomegaly, and developmental delay than type 1. Our case, a 29-year-old male, had shown normal development up to the age of 12 years and 5 months. Subsequently, he developed ataxia and myoclonus. At age 12 years and 11 months, generalized tonic-clonic seizures occurred with ataxia, myoclonus, intentional tremor, borderline intelligence, and cherry-red macular spot. Skin fibroblast enzymological analysis of neuraminidase yielded a value below 1 nmol/h/mg protein. NEU1 gene findings were consistent with compound heterozygous missense variant c.1034C>T(p.Thr345Ile) and c.239C>T(p.Pro80Leu), while electron microscopy of skinfibroblasts showed vacuoles and dense body deposition in both neuroblasts and Schwann cells. In addition, this is the first reported case of sialidosis type 1 associated with a quadricuspid aortic valve malformation. Collectively, the above findings indicated a diagnosis of sialidosis type 1 with cardiac malformation. The involuntary movement improved temporarily in response to clonazepam but then gradually worsened. During 17 years of follow-up, his seizures were controlled with anticonvulsants, but the ataxia, myoclonus and intentional tremor gradually worsened.
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