Sialidosis type 1

Mendelian MONDO:0019346 Pathograph 36 Lysosomal Storage Disorder Oligosaccharidosis Mucolipidosis

Sialidosis type 1 is an ultra-rare autosomal recessive lysosomal storage disorder caused by biallelic pathogenic variants in NEU1, encoding lysosomal neuraminidase 1. Residual but insufficient lysosomal sialidase activity impairs degradation of sialylated glycoproteins and oligosaccharides, causing sialylated metabolite accumulation with adolescent or young-adult onset of progressive myoclonus, ataxia, seizures, visual impairment, and macular cherry-red spots.

Ask OpenScientist

Ask a research question about Sialidosis type 1. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).

Submitting...

Do not include personal health information in your question. Questions and results are cached in your browser's local storage.

1
Mappings
2
Definitions
1
Inheritance
5
Pathophys.
1
Histopath.
20
Phenotypes
36
Pathograph
1
Genes
8
Treatments
12
References
1
Deep Research
🔗

Mappings

MONDO
MONDO:0019346 sialidosis type 1
skos:exactMatch Orphanet ORPHA:812
Orphanet ORPHA:812 lists MONDO:0019346 as an exact cross-reference for sialidosis type 1.
📘

Definitions

2
Orphanet Sialidosis type 1 definition
A very rare, normosomatic lysosomal storage disease characterized by gait abnormalities, progressive visual loss, bilateral macular cherry-red spots, myoclonic epilepsy, and ataxia, usually presenting in the second to third decade.
OTHER
Show evidence (2 references)
ORPHA:812 SUPPORT Other
"Sialidosis type 1 (ST-1) is a very rare lysosomal storage disease"
Orphanet defines Sialidosis type 1 as a very rare lysosomal storage disease.
PMID:41665440 SUPPORT Human Clinical
"progressive lysosomal storage disorder caused by pathogenic variants in NEU1."
The contemporary clinical review supports the genetic and lysosomal-disease framing.
Type 1/Type 2 clinical distinction
Sialidosis type 1 is the normomorphic or mild form, whereas dysmorphic somatic features such as coarse facies, hepatosplenomegaly, and dysostosis multiplex belong to the more severe type 2 presentation unless supported by direct type 1 evidence.
OTHER
Show evidence (3 references)
PMID:32453490 SUPPORT Human Clinical
"sialidosis type 1 (normomorphic or mild form) and sialidosis type 2 (dysmorphic or severe form)"
The clinical cohort explicitly distinguishes the normomorphic Type 1 form from the dysmorphic Type 2 form.
PMID:32453490 SUPPORT Human Clinical
"They have no obvious physical defects, and their intelligence is either not impaired or slightly impaired generally."
The Type 1 description supports excluding unsupported dysmorphic and skeletal Type 2 features.
PMID:32453490 SUPPORT Human Clinical
"Sialidosis type 2 is more severe and presents earlier with abnormal somatic features, including coarse facial features, hepatosplenomegaly, dysostosis multiplex, developmental delay and mental retardation"
The same source identifies dysmorphic and skeletal findings as Type 2 features rather than unqualified Type 1 features.
👪

Inheritance

1
Autosomal recessive inheritance HP:0000007
Sialidosis type 1 is inherited in an autosomal recessive pattern.
Autosomal recessive inheritance
Show evidence (2 references)
ORPHA:812 SUPPORT Other
"Autosomal recessive"
Orphanet records autosomal recessive inheritance for Sialidosis type 1.
PMID:41665440 SUPPORT Human Clinical
"Sialidosis type I (ST-1) is an autosomal-recessive, very rare,"
The review explicitly describes autosomal recessive inheritance.
⚙

Pathophysiology

5
NEU1 lysosomal neuraminidase deficiency
Biallelic NEU1 pathogenic variants reduce lysosomal neuraminidase 1 activity. Because NEU1 normally removes terminal sialic-acid residues from glycoproteins and oligosaccharides in the lysosome, deficient activity impairs lysosomal glycoprotein catabolism.
Neuron link Fibroblast link
NEU1 link
glycoprotein catabolic process link ↓ DECREASED
exo-alpha-sialidase activity link ↓ DECREASED
Lysosome link
Downstream
Sialylated metabolite lysosomal storage Deficient lysosomal NEU1 blocks processing of sialylated glycoproteins and oligosaccharides, producing sialylated storage metabolites.
Show evidence (2 references)
PMID:32143456 SUPPORT In Vitro
"Congenital deficiency of the lysosomal sialidase neuraminidase 1 (NEU1) causes"
The study identifies deficient lysosomal NEU1 activity as causal for sialidosis.
PMID:28138907 SUPPORT Human Clinical
"deficiency of neuraminidase. Genetic analysis identified novel homozygous"
Patient enzyme testing directly supports neuraminidase deficiency in Sialidosis type 1.
Residual mild NEU1 variant activity
Sialidosis type 1 generally reflects variant combinations retaining some catalytic activity. Residual activity distinguishes the attenuated type I phenotype from severe catalytically inactive type II combinations, and variant-specific folding, trafficking, and local structural effects influence clinical severity.
exo-alpha-sialidase activity link ↓ DECREASED
Lysosome link
Downstream
NEU1 lysosomal neuraminidase deficiency Mild but catalytically impaired NEU1 variants produce the residual neuraminidase deficiency underlying the type 1 phenotype.
Show evidence (2 references)
PMID:38600684 SUPPORT Human Clinical
"sialidosis type 1 has at least one catalytically active (mild)"
The genotype-structure-phenotype study states that type I retains at least one catalytically active variant.
PMID:10944856 SUPPORT In Vitro
"V217M mutation was partly transported to lysosomes and showed residual enzyme"
Functional studies of patient variants support residual activity and abnormal trafficking as determinants of type I disease.
Sialylated metabolite lysosomal storage
Impaired lysosomal degradation of sialylated glycoconjugates causes accumulation of sialylated metabolites in tissues and body fluids, including abnormal urinary sialylated oligosaccharides and O-linked sialopeptides.
glycoprotein catabolic process link ↓ DECREASED amino sugar metabolic process link ⚠ ABNORMAL
Lysosome link
Downstream
Neuronal lysosomal storage and gliosis Nervous-system lysosomal storage is associated with glial LAMP1 accumulation, astrogliosis, and the progressive neurologic syndrome.
Retinal ganglion cell layer storage Sialyloligosaccharide accumulation in perifoveal ganglion-cell and retinal nerve-fiber layers produces the characteristic retinal pathology.
Urinary excretion of sialylated oligosaccharides Systemic sialylated metabolite storage is reflected by increased urinary sialylated oligosaccharide excretion.
Increased urinary O-linked sialopeptides Impaired lysosomal sialylated substrate catabolism produces urinary O-linked sialopeptide accumulation.
Cataract Accumulated abnormal metabolic products in ocular tissues contribute to punctate cataracts.
Corneal opacity Ocular metabolic-product accumulation can manifest as corneal clouding.
Show evidence (2 references)
PMID:32143456 SUPPORT In Vitro
"accumulation of sialylated metabolites in tissues and body fluids."
The therapy study states the biochemical storage consequence of NEU1 deficiency.
ORPHA:812 SUPPORT Other
"HP:0012061 | Urinary excretion of sialylated oligosaccharides | Very frequent (99-80%)"
Orphanet records urinary sialylated oligosaccharide excretion as very frequent.
Neuronal lysosomal storage and gliosis
Sialylated storage in the nervous system is associated with glial lysosomal pathology and impaired motor function in Neu1-deficient models, while human Type 1 disease presents with progressive ataxia, myoclonic seizures, and related neurologic manifestations.
Neuron link Astrocyte link Microglial cell link
nervous system process link ⚠ ABNORMAL
Brain link
Downstream
Seizure Progressive neuronal storage and glial pathology cause network dysfunction that manifests as seizures.
Generalized myoclonic seizure Neural storage-related cortical hyperexcitability manifests as progressive myoclonic seizures.
Ataxia Nervous-system storage and gliosis disrupt cerebellar and motor circuitry, causing ataxia.
Gait disturbance Progressive ataxia and motor dysfunction produce gait impairment.
Decreased nerve conduction velocity Peripheral nervous system involvement in type 1 can include decreased nerve conduction velocity.
Myoclonus Progressive cortical and motor network dysfunction produces myoclonus.
Tremor Motor circuit involvement can manifest as intentional tremor.
Dysarthria Progressive motor and cerebellar pathway involvement can impair speech articulation.
Hyperreflexia Central motor pathway involvement can manifest as hyperreflexia.
EEG abnormality Epileptic network dysfunction can produce diffuse spike-wave EEG abnormalities.
Cerebellar atrophy Progressive neural storage disease can be accompanied by cerebellar and brain atrophy.
Show evidence (2 references)
PMID:38321198 SUPPORT Model Organism
"Untreated Neu1-/- mice showed astrogliosis and microglial"
The Neu1-deficient mouse model supports lysosomal neurologic pathology with glial activation.
PMID:41665440 SUPPORT Human Clinical
"is clinically characterized by progressive ataxia, myoclonic seizures (MS),"
The review identifies progressive ataxia and myoclonic seizures as core clinical features.
Retinal ganglion cell layer storage
In Type 1 disease, sialyloligosaccharide and related metabolic-product accumulation in the perifoveal ganglion cell layer and retinal nerve fiber layer produces OCT/FAF abnormalities and the macular cherry-red spot.
Retinal ganglion cell link
visual perception link ⚠ ABNORMAL
Retina link
Downstream
Retinopathy Ganglion-cell and retinal nerve fiber layer storage produces retinal OCT abnormalities.
Visual impairment Retinal and visual-pathway storage abnormalities impair visual function.
Progressive visual loss Progressive retinal and visual-pathway involvement causes worsening vision.
Nystagmus Visual pathway impairment can manifest with nystagmus.
Cherry red spot of the macula Perifoveal ganglion-cell and RNFL storage creates the macular cherry-red spot.
Show evidence (2 references)
PMID:32453490 SUPPORT Human Clinical
"The appearance of macular cherry red spots is caused by the accumulation of sialyloligosaccharides in the perifoveal ganglion cell layer and RNFL."
The clinical Type 1 cohort explains the retinal storage basis of cherry-red spots.
PMID:32453490 SUPPORT Human Clinical
"Accumulation of metabolic products in the lens, ganglion cell, and RNFL are characteristic ocular findings"
The cohort identifies lens, ganglion-cell, and RNFL metabolic-product accumulation as characteristic ocular pathology.
✶

Histopathology

1
Retinal ganglion cell and nerve fiber layer storage
OCT and fundus-autofluorescence findings in Type 1 disease reflect storage-related abnormality in the perifoveal ganglion cell layer and retinal nerve fiber layer.
Show evidence (2 references)
PMID:32453490 SUPPORT Human Clinical
"The appearance of macular cherry red spots is caused by the accumulation of sialyloligosaccharides in the perifoveal ganglion cell layer and RNFL."
The Type 1 cohort identifies the cellular retinal storage basis of the macular cherry-red spot.
PMID:32453490 SUPPORT Human Clinical
"OCT showed increased reflectivity in the retinal nerve fiber layer (RNFL) and ganglion cell layer in all patients."
OCT evidence supports a microscopic/cellular retinal finding in Type 1 disease.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Sialidosis type 1 Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

20
Cardiovascular 1
Cherry red spot of the macula FREQUENT Cherry red spot of the macula (HP:0010729)
Show evidence (2 references)
PMID:32453490 SUPPORT Human Clinical
"Macular cherry red spots are a distinctive feature of the ocular manifestation of sialidosis type 1."
The Type 1 ophthalmic cohort identifies cherry-red spots as a distinctive ocular feature.
PMID:32453490 SUPPORT Human Clinical
"According to the 45 genetically confirmed sialidosis type 1 cases, macular cherry red spots were observed in only 51.2% (22/43) of the patients"
The literature review within the cohort supports a frequent, not universal, frequency estimate.
Eye 6
Retinopathy VERY_FREQUENT Retinopathy (HP:0000488)
Show evidence (1 reference)
PMID:32453490 SUPPORT Human Clinical
"OCT showed increased reflectivity in the retinal nerve fiber layer (RNFL) and ganglion cell layer in all patients."
The Type 1 ophthalmic cohort supports retinopathy with OCT abnormalities in all patients.
Visual impairment VERY_FREQUENT Visual impairment (HP:0000505)
Show evidence (1 reference)
PMID:32453490 SUPPORT Human Clinical
"On ophthalmological assessment, all patients presented with visual impairment."
The Type 1 cohort documents visual impairment in all four patients.
Cataract Cataract (HP:0000518)
Show evidence (1 reference)
PMID:32453490 SUPPORT Human Clinical
"Punctate cataracts were found in all patients"
The Type 1 ophthalmic cohort supports cataract as a recurrent ocular manifestation.
Progressive visual loss Progressive visual loss (HP:0000529)
Show evidence (1 reference)
PMID:32453490 SUPPORT Human Clinical
"Patients with sialidosis type 1 typically present progressive myoclonus epilepsy (PME) in their second or third decade of life, as well as progressive impaired vision and macular cherry red spots."
The Type 1 review section identifies progressive impaired vision as a typical manifestation.
Nystagmus FREQUENT Nystagmus (HP:0000639)
Show evidence (1 reference)
PMID:32453490 SUPPORT Human Clinical
"Severe nystagmus was found in two patients."
The Type 1 cohort documents nystagmus in two of four patients.
Corneal opacity Corneal opacity (HP:0007957)
Show evidence (1 reference)
PMID:32453490 SUPPORT Human Clinical
"punctate cataract and corneal clouding are considered to be characteristic ophthalmic signs"
The Type 1 ophthalmic cohort review supports corneal clouding as an ophthalmic sign.
Nervous System 10
Seizure FREQUENT Seizure (HP:0001250)
Show evidence (2 references)
PMID:32453490 SUPPORT Human Clinical
"A total of 75% (3/4) of patients developed seizures and cerebellar ataxia."
The Type 1 cohort supports seizures in three of four patients.
PMID:41665440 SUPPORT Human Clinical
"bilateral tonic-clonic seizures (BTCS), and distinctive ophthalmological"
The 2026 treatment review identifies myoclonic and bilateral tonic-clonic seizures as core features.
Generalized myoclonic seizure FREQUENT Generalized myoclonic seizure (HP:0002123)
Show evidence (2 references)
PMID:32453490 SUPPORT Human Clinical
"Three out of four patients presented progressive myoclonus epilepsy."
The Type 1 cohort supports progressive myoclonus epilepsy in three of four patients.
PMID:41665440 SUPPORT Human Clinical
"is clinically characterized by progressive ataxia, myoclonic seizures (MS),"
The 2026 review identifies myoclonic seizures as a core Type 1 manifestation.
Ataxia FREQUENT Ataxia (HP:0001251)
Show evidence (2 references)
PMID:32453490 SUPPORT Human Clinical
"A total of 75% (3/4) of patients developed seizures and cerebellar ataxia."
The Type 1 cohort supports cerebellar ataxia in three of four patients.
PMID:28138907 SUPPORT Human Clinical
"The patient developed ataxia and myoclonus at 9 y of age."
The case report supports ataxia as a Type 1 manifestation.
Gait disturbance Gait disturbance (HP:0001288)
Show evidence (2 references)
ORPHA:812 SUPPORT Other
"HP:0001288 | Gait disturbance | Very frequent (99-80%)"
Orphanet records gait disturbance for Sialidosis type 1.
PMID:23291686 SUPPORT Human Clinical
"myoclonus, intentional tremors, limb and gait ataxia, hyperreflexia and macular"
The Type 1 case report supports gait ataxia.
Myoclonus FREQUENT Myoclonus (HP:0001336)
Show evidence (2 references)
PMID:32453490 SUPPORT Human Clinical
"On neurological assessment, 75% (3/4) of patients had a history of progressive myoclonus"
The Type 1 cohort documents progressive myoclonus in three of four patients.
PMID:33121223 SUPPORT Human Clinical
"sialidosis type I with a typical presentation of progressive cortical myoclonus"
Genetically confirmed cases support progressive cortical myoclonus as a typical presentation.
Tremor Tremor (HP:0001337)
Show evidence (1 reference)
PMID:23291686 SUPPORT Human Clinical
"myoclonus, intentional tremors, limb and gait ataxia, hyperreflexia and macular"
The Type 1 case report supports intentional tremor.
Dysarthria Dysarthria (HP:0001260)
Show evidence (2 references)
PMID:23291686 SUPPORT Human Clinical
"to our hospital at age 16. On admission, subnormal intelligence, dysarthria,"
The Type 1 case report documents dysarthria.
PMID:32453490 SUPPORT Human Clinical
"evolving to slurred speech and dysphagia in the late stage."
The Type 1 cohort supports progressive speech involvement in late-stage disease.
Hyperreflexia Hyperreflexia (HP:0001347)
Show evidence (1 reference)
PMID:23291686 SUPPORT Human Clinical
"myoclonus, intentional tremors, limb and gait ataxia, hyperreflexia and macular"
The Type 1 case report documents hyperreflexia.
EEG abnormality FREQUENT EEG abnormality (HP:0002353)
Show evidence (1 reference)
PMID:32453490 SUPPORT Human Clinical
"EEG showed different extents of diffuse paroxysmal features as spike‐wave complexes in two patients."
The Type 1 cohort documents EEG abnormalities in two of four patients.
Cerebellar atrophy Cerebellar atrophy (HP:0001272)
Show evidence (2 references)
PMID:10686466 SUPPORT Human Clinical
"showed severe atrophy of the cerebellum and pontine region"
The Type I study documents cerebellar atrophy.
PMID:23291686 SUPPORT Human Clinical
"Serial brain MRI showed diffuse brain atrophy progressing rapidly"
Serial imaging supports progressive neurodegeneration in some Type I patients.
Other 3
Decreased nerve conduction velocity FREQUENT Decreased nerve conduction velocity (HP:0000762)
Show evidence (1 reference)
ORPHA:812 SUPPORT Other
"HP:0000762 | Decreased nerve conduction velocity | Frequent (79-30%)"
Orphanet provides the disease-phenotype association and frequency band.
Increased urinary O-linked sialopeptides VERY_FREQUENT Increased urinary O-linked sialopeptides (HP:0003461)
Show evidence (1 reference)
ORPHA:812 SUPPORT Other
"HP:0003461 | Increased urinary O-linked sialopeptides | Very frequent (99-80%)"
Orphanet records increased urinary O-linked sialopeptides for Sialidosis type 1.
Urinary excretion of sialylated oligosaccharides VERY_FREQUENT Urinary excretion of sialylated oligosaccharides (HP:0012061)
Show evidence (2 references)
ORPHA:812 SUPPORT Other
"HP:0012061 | Urinary excretion of sialylated oligosaccharides | Very frequent (99-80%)"
Orphanet records urinary sialylated oligosaccharide excretion as very frequent.
PMID:32453490 SUPPORT Human Clinical
"urinary excretion of sialylated oligosaccharides"
The Type 1 cohort review links NEU1 deficiency to urinary sialylated oligosaccharide excretion.
🧬

Genetic Associations

1
Biallelic NEU1 pathogenic variants (Causative)
Autosomal recessive inheritance
Show evidence (3 references)
ORPHA:812 SUPPORT Other
"NEU1 | neuraminidase 1 | hgnc:7758 | Disease-causing germline mutation(s) in"
Orphanet identifies NEU1 as the disease-causing gene for Sialidosis type 1.
PMID:28138907 SUPPORT Human Clinical
"Genetic analysis identified novel homozygous"
The case report identifies a homozygous NEU1 variant in a patient with Sialidosis type 1.
PMID:38600684 SUPPORT Human Clinical
"a newly reported family carrying N-acetyl-α-neuraminidase-1"
The study reports a family with NEU1 variants causing Sialidosis type 1.
💊

Treatments

8
Antiseizure pharmacotherapy for myoclonic and bilateral tonic-clonic seizures
Action: Pharmacotherapy NCIT:C15986
Agent: acetazolamide ↗ perampanel ↗ levetiracetam ↗ valproate ↗ clonazepam ↗ zonisamide ↗
Symptomatic antiseizure treatment may reduce myoclonic seizures and bilateral tonic-clonic seizures, although data remain too limited for standardized guidelines.
Target Phenotypes: Seizure ↗ Myoclonus ↗
Show evidence (2 references)
PMID:41665440 SUPPORT Human Clinical
"CZP, and ZNS, demonstrated fairly consistent efficacy in managing MS and BTCS."
The 2026 multicenter analysis reports fairly consistent seizure-management efficacy for several antiseizure medications.
PMID:41665440 SUPPORT Human Clinical
"define standardized treatment guidelines, some ASMs, such as ACZ, PER, LEV, VPA,"
The review limits the strength of treatment recommendations despite symptomatic benefit.
Sodium oxybate for refractory myoclonic seizures
Action: Pharmacotherapy NCIT:C15986
Agent: Sodium Oxybate ↗
Sodium oxybate may be considered for refractory disabling myoclonic seizures in selected Sialidosis type 1 cases, but the evidence remains limited and non-standardized.
Target Phenotypes: Generalized myoclonic seizure ↗ Myoclonus ↗
Show evidence (1 reference)
PMID:41665440 PARTIAL Human Clinical
"Sodium oxybate or deep-brain stimulation may be considered in refractory cases."
The multicenter review lists sodium oxybate as a consideration for refractory cases, without establishing standardized efficacy.
Deep-brain stimulation for refractory myoclonic seizures
Action: deep brain stimulation MAXO:0000943
Deep-brain stimulation is a refractory-case option mentioned in the 2026 treatment review; it is not established as routine therapy for Sialidosis type 1.
Target Phenotypes: Generalized myoclonic seizure ↗ Myoclonus ↗
Show evidence (1 reference)
PMID:41665440 PARTIAL Human Clinical
"Sodium oxybate or deep-brain stimulation may be considered in refractory cases."
The multicenter review lists deep-brain stimulation as a consideration for refractory cases, without establishing standardized efficacy.
Supportive multidisciplinary care
Action: supportive care MAXO:0000950
Supportive management addresses progressive movement impairment, visual impairment, seizures, rehabilitation needs, and developmental or educational support in the absence of an approved curative therapy.
Target Phenotypes: Ataxia ↗ Progressive visual loss ↗
Show evidence (2 references)
PMID:41665440 SUPPORT Human Clinical
"Given the lack of curative options, in this study, we investigated"
The review supports symptomatic management in the absence of curative options.
PMID:32143456 SUPPORT In Vitro
"for which no therapy is currently available."
The therapy study supports the absence of an established disease-modifying therapy.
Investigational betaine and PPCA-based therapeutic strategies
Action: Pharmacotherapy NCIT:C15986
Agent: glycine betaine ↗
Preclinical and patient-fibroblast experiments suggest that PPCA-based chaperone approaches and selected dietary or pharmacologic compounds, including betaine, can increase residual mutant NEU1 activity, but these remain investigational.
Mechanism Target:
RESTORES NEU1 lysosomal neuraminidase deficiency — PPCA and selected compounds are intended to increase residual mutant NEU1 activity.
Show evidence (1 reference)
PMID:32143456 PARTIAL In Vitro
"primary fibroblasts. We observed a small, but consistent increase in NEU1"
Patient fibroblast experiments support partial restoration of residual NEU1 activity.
Show evidence (1 reference)
PMID:32143456 PARTIAL Model Organism
"increased the levels of mutant NEU1 and resolved the"
Mouse-model data suggest betaine can improve mutant NEU1 levels and oligosacchariduria, but this remains preclinical.
Investigational AAV9 NEU1 and CTSA gene therapy
Action: gene therapy MAXO:0001001
AAV-mediated coexpression of NEU1 and CTSA/PPCA is a preclinical strategy intended to restore lysosomal NEU1 activity and reduce neurologic pathology; current support comes from mouse studies rather than human trials.
Mechanism Target:
RESTORES NEU1 lysosomal neuraminidase deficiency — AAV9-P3-NP delivers NEU1 and CTSA cDNAs to restore lysosomal NEU1 function.
Show evidence (1 reference)
PMID:38321198 SUPPORT Model Organism
"The vector, AAV9-P3-NP, included the human NEU1 promoter, NEU1 cDNA,"
The mouse study describes the NEU1/CTSA AAV vector design.
Show evidence (1 reference)
PMID:38321198 SUPPORT Model Organism
"decreased astrogliosis and LAMP1 accumulation in the nervous system"
The Neu1 knockout mouse study supports neurologic-pathology improvement after AAV treatment.
Hematopoietic cell transplantation
Action: hematopoietic stem cell transplantation MAXO:0000747
Hematopoietic cell transplantation has been reported in one adolescent with Sialidosis type 1. Biomarkers improved after engraftment, but motor decline continued, so this remains a highly selected and uncertain intervention.
Mechanism Target:
MODULATES Sialylated metabolite lysosomal storage — Donor engraftment was associated with plasma and urine biomarker response.
Show evidence (1 reference)
PMID:35242566 PARTIAL Human Clinical
"plasma and urine biomarkers responded concurrently with engraftment."
The single case report supports biomarker response after BMT.
Show evidence (1 reference)
PMID:35242566 PARTIAL Human Clinical
"overall decline in motor performance."
The same case report limits evidence strength because neurologic motor performance still declined.
Genetic counseling
Action: genetic counseling MAXO:0000079
Genetic counseling supports recurrence-risk assessment and family planning for autosomal recessive NEU1-associated disease.
Show evidence (1 reference)
ORPHA:812 SUPPORT Other
"Autosomal recessive"
Autosomal recessive inheritance supports genetic counseling for recurrence risk.
🔬

Biochemical Markers

3
Reduced neuraminidase activity (Reduced)
Context: Diagnostic enzymatic defect
Pathograph Readouts
Readout Of NEU1 lysosomal neuraminidase deficiency Negative Diagnostic
Reduced lysosomal neuraminidase activity is the diagnostic enzymatic readout of deficient NEU1 function.
Show evidence (1 reference)
PMID:28138907 SUPPORT Human Clinical
"deficiency of neuraminidase. Genetic analysis identified novel homozygous"
Patient enzyme and molecular testing support reduced neuraminidase activity as the biochemical readout of NEU1 deficiency.
Show evidence (2 references)
PMID:28138907 SUPPORT Human Clinical
"deficiency of neuraminidase. Genetic analysis identified novel homozygous"
Patient enzyme analysis supports neuraminidase deficiency as the diagnostic defect.
PMID:38600684 SUPPORT In Vitro
"a sialidase activity assay. Cherry-red spots were more prevalent in the"
Functional activity testing supports variant-specific sialidase deficiency.
Urinary sialylated oligosaccharides (Elevated)
Context: Diagnostic urinary storage biomarker
Pathograph Readouts
Readout Of Sialylated metabolite lysosomal storage Positive Diagnostic
Elevated urinary sialylated oligosaccharides report systemic accumulation of sialylated storage metabolites.
Show evidence (1 reference)
PMID:32453490 SUPPORT Human Clinical
"leading to abnormal tissue accumulation as well as urinary excretion of sialylated oligosaccharides"
The type 1 cohort review links the storage mechanism to urinary sialylated oligosaccharide excretion.
Show evidence (2 references)
ORPHA:812 SUPPORT Other
"HP:0012061 | Urinary excretion of sialylated oligosaccharides | Very frequent (99-80%)"
Orphanet records urinary sialylated oligosaccharide excretion as very frequent.
PMID:32143456 SUPPORT In Vitro
"accumulation of sialylated metabolites in tissues and body fluids."
The study supports sialylated metabolite accumulation as the biochemical storage signature.
Urinary O-linked sialopeptides (Elevated)
Context: Diagnostic urinary storage biomarker
Pathograph Readouts
Readout Of Sialylated metabolite lysosomal storage Positive Diagnostic
Increased urinary O-linked sialopeptides are a diagnostic readout of sialylated lysosomal storage in Sialidosis type 1.
Show evidence (1 reference)
ORPHA:812 SUPPORT Other
"HP:0003461 | Increased urinary O-linked sialopeptides | Very frequent (99-80%)"
Orphanet records increased urinary O-linked sialopeptides as a very frequent biochemical manifestation, supporting this urinary marker as a readout of the storage node.
Show evidence (1 reference)
ORPHA:812 SUPPORT Other
"HP:0003461 | Increased urinary O-linked sialopeptides | Very frequent (99-80%)"
Orphanet records this urinary glycopeptide abnormality as very frequent.
{ }

Source YAML

click to show 
name: Sialidosis type 1
category: Mendelian
creation_date: "2026-05-04T18:28:00Z"
updated_date: "2026-05-21T06:02:38Z"
synonyms:
- Cherry-red spot-myoclonus syndrome
- Lipomucopolysaccharidosis
- Normomorphic sialidosis
- Sialidosis type I
description: >
  Sialidosis type 1 is an ultra-rare autosomal recessive lysosomal storage
  disorder caused by biallelic pathogenic variants in NEU1, encoding lysosomal
  neuraminidase 1. Residual but insufficient lysosomal sialidase activity
  impairs degradation of sialylated glycoproteins and oligosaccharides, causing
  sialylated metabolite accumulation with adolescent or young-adult onset of
  progressive myoclonus, ataxia, seizures, visual impairment, and macular
  cherry-red spots.
disease_term:
  preferred_term: sialidosis type 1
  term:
    id: MONDO:0019346
    label: sialidosis type 1
parents:
- Lysosomal Storage Disorder
- Oligosaccharidosis
- Mucolipidosis
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0019346
      label: sialidosis type 1
    mapping_predicate: skos:exactMatch
    mapping_source: Orphanet ORPHA:812
    mapping_justification: >
      Orphanet ORPHA:812 lists MONDO:0019346 as an exact cross-reference for
      sialidosis type 1.
external_assertions:
- name: Orphanet Sialidosis type 1 disease record
  source: Orphanet
  assertion_type: structured_disease_record
  external_id: ORPHA:812
  url: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=812
  description: >
    Orphanet's ORPHA:812 structured record for Sialidosis type 1 provides the
    exact MONDO cross-reference, OMIM cross-reference, definition, autosomal
    recessive inheritance, epidemiology, NEU1 gene association, and HPO
    phenotype annotations reconciled against Type 1 primary literature in this entry.
  evidence:
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "MONDO:0019346 | Exact"
    explanation: Orphanet maps ORPHA:812 to the same MONDO identifier used by this entry.
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "OMIM:256550 | Narrower"
    explanation: Orphanet lists OMIM:256550 as an external cross-reference.
definitions:
- name: Orphanet Sialidosis type 1 definition
  definition_type: OTHER
  description: >
    A very rare, normosomatic lysosomal storage disease characterized by gait
    abnormalities, progressive visual loss, bilateral macular cherry-red spots,
    myoclonic epilepsy, and ataxia, usually presenting in the second to third
    decade.
  evidence:
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Sialidosis type 1 (ST-1) is a very rare lysosomal storage disease"
    explanation: Orphanet defines Sialidosis type 1 as a very rare lysosomal storage disease.
  - reference: PMID:41665440
    reference_title: "Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "progressive lysosomal storage disorder caused by pathogenic variants in NEU1."
    explanation: The contemporary clinical review supports the genetic and lysosomal-disease framing.
- name: Type 1/Type 2 clinical distinction
  definition_type: OTHER
  description: >
    Sialidosis type 1 is the normomorphic or mild form, whereas dysmorphic
    somatic features such as coarse facies, hepatosplenomegaly, and dysostosis
    multiplex belong to the more severe type 2 presentation unless supported by
    direct type 1 evidence.
  evidence:
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "sialidosis type 1 (normomorphic or mild form) and sialidosis type 2 (dysmorphic or severe form)"
    explanation: The clinical cohort explicitly distinguishes the normomorphic Type 1 form from the dysmorphic Type 2 form.
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "They have no obvious physical defects, and their intelligence is either not impaired or slightly impaired generally."
    explanation: The Type 1 description supports excluding unsupported dysmorphic and skeletal Type 2 features.
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Sialidosis type 2 is more severe and presents earlier with abnormal somatic features, including coarse facial features, hepatosplenomegaly, dysostosis multiplex, developmental delay and mental retardation"
    explanation: The same source identifies dysmorphic and skeletal findings as Type 2 features rather than unqualified Type 1 features.
inheritance:
- name: Autosomal recessive inheritance
  description: Sialidosis type 1 is inherited in an autosomal recessive pattern.
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  evidence:
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Autosomal recessive"
    explanation: Orphanet records autosomal recessive inheritance for Sialidosis type 1.
  - reference: PMID:41665440
    reference_title: "Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Sialidosis type I (ST-1) is an autosomal-recessive, very rare,"
    explanation: The review explicitly describes autosomal recessive inheritance.
prevalence:
- population: Europe
  percentage: Ultra-rare
  notes: >
    Orphanet records European point prevalence and prevalence at birth below
    1 per 1,000,000; a 2026 review also describes ST-1 as very rare.
  evidence:
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "<1 / 1 000 000 | Europe | Point prevalence | ORPHANET"
    explanation: Orphanet's epidemiology table supports the ultra-rare European point-prevalence framing.
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "<1 / 1 000 000 | Europe | Prevalence at birth | ORPHANET"
    explanation: Orphanet records European prevalence at birth below 1 per 1,000,000.
progression:
- phase: Late childhood or adolescent onset progressive neurologic disease
  age_range: Childhood to adolescence
  notes: >
    Type 1 disease usually begins in late childhood, adolescence, or young
    adulthood with progressive myoclonus, ataxia, gait impairment, seizures,
    and visual decline. Imaging may remain normal early but can later show
    progressive brain or cerebellar atrophy in some patients.
  evidence:
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Age of onset: Adolescent"
    explanation: Orphanet records adolescent onset for Sialidosis type 1.
  - reference: PMID:28138907
    reference_title: Sialidosis Type 1 with a Novel Mutation in the Neuraminidase-1 (NEU1) Gene.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The patient developed ataxia and myoclonus at 9 y of age."
    explanation: The case report documents childhood onset of core neurologic manifestations.
  - reference: PMID:23291686
    reference_title: Clinical and serial MRI findings of a sialidosis type I patient with a novel missense mutation in the NEU1 gene.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Serial brain MRI showed diffuse brain atrophy progressing rapidly"
    explanation: Serial MRI in a type I patient supports progressive neurodegeneration in some cases.
pathophysiology:
- name: NEU1 lysosomal neuraminidase deficiency
  description: >
    Biallelic NEU1 pathogenic variants reduce lysosomal neuraminidase 1
    activity. Because NEU1 normally removes terminal sialic-acid residues from
    glycoproteins and oligosaccharides in the lysosome, deficient activity
    impairs lysosomal glycoprotein catabolism.
  cell_types:
  - preferred_term: Neuron
    term:
      id: CL:0000540
      label: neuron
  - preferred_term: Fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  genes:
  - preferred_term: NEU1
    term:
      id: hgnc:7758
      label: NEU1
  molecular_functions:
  - preferred_term: exo-alpha-sialidase activity
    term:
      id: GO:0004308
      label: exo-alpha-sialidase activity
    modifier: DECREASED
  biological_processes:
  - preferred_term: glycoprotein catabolic process
    term:
      id: GO:0006516
      label: glycoprotein catabolic process
    modifier: DECREASED
  locations:
  - preferred_term: Lysosome
    term:
      id: GO:0005764
      label: lysosome
  evidence:
  - reference: PMID:32143456
    reference_title: Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Congenital deficiency of the lysosomal sialidase neuraminidase 1 (NEU1) causes"
    explanation: The study identifies deficient lysosomal NEU1 activity as causal for sialidosis.
  - reference: PMID:28138907
    reference_title: Sialidosis Type 1 with a Novel Mutation in the Neuraminidase-1 (NEU1) Gene.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "deficiency of neuraminidase. Genetic analysis identified novel homozygous"
    explanation: Patient enzyme testing directly supports neuraminidase deficiency in Sialidosis type 1.
  downstream:
  - target: Sialylated metabolite lysosomal storage
    description: Deficient lysosomal NEU1 blocks processing of sialylated glycoproteins and oligosaccharides, producing sialylated storage metabolites.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:32143456
      reference_title: Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: "processing/degradation of sialo-glycoproteins and sialo-oligosaccharides"
      explanation: The study links NEU1 deficiency to impaired degradation of sialylated substrates.
- name: Residual mild NEU1 variant activity
  description: >
    Sialidosis type 1 generally reflects variant combinations retaining some
    catalytic activity. Residual activity distinguishes the attenuated type I
    phenotype from severe catalytically inactive type II combinations, and
    variant-specific folding, trafficking, and local structural effects influence
    clinical severity.
  molecular_functions:
  - preferred_term: exo-alpha-sialidase activity
    term:
      id: GO:0004308
      label: exo-alpha-sialidase activity
    modifier: DECREASED
  locations:
  - preferred_term: Lysosome
    term:
      id: GO:0005764
      label: lysosome
  evidence:
  - reference: PMID:38600684
    reference_title: Clinical and Structural Characteristics of NEU1 Variants Causing Sialidosis Type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "sialidosis type 1 has at least one catalytically active (mild)"
    explanation: The genotype-structure-phenotype study states that type I retains at least one catalytically active variant.
  - reference: PMID:10944856
    reference_title: Molecular and structural studies of Japanese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "V217M mutation was partly transported to lysosomes and showed residual enzyme"
    explanation: Functional studies of patient variants support residual activity and abnormal trafficking as determinants of type I disease.
  downstream:
  - target: NEU1 lysosomal neuraminidase deficiency
    description: Mild but catalytically impaired NEU1 variants produce the residual neuraminidase deficiency underlying the type 1 phenotype.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:10944856
      reference_title: Molecular and structural studies of Japanese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: "the data, we surmise that the V217M substitution may be closely associated with"
      explanation: Variant residual activity is associated with late-onset, moderate type I phenotype.
- name: Sialylated metabolite lysosomal storage
  description: >
    Impaired lysosomal degradation of sialylated glycoconjugates causes
    accumulation of sialylated metabolites in tissues and body fluids, including
    abnormal urinary sialylated oligosaccharides and O-linked sialopeptides.
  biological_processes:
  - preferred_term: glycoprotein catabolic process
    term:
      id: GO:0006516
      label: glycoprotein catabolic process
    modifier: DECREASED
  - preferred_term: amino sugar metabolic process
    term:
      id: GO:0006040
      label: amino sugar metabolic process
    modifier: ABNORMAL
  locations:
  - preferred_term: Lysosome
    term:
      id: GO:0005764
      label: lysosome
  evidence:
  - reference: PMID:32143456
    reference_title: Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "accumulation of sialylated metabolites in tissues and body fluids."
    explanation: The therapy study states the biochemical storage consequence of NEU1 deficiency.
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0012061 | Urinary excretion of sialylated oligosaccharides | Very frequent (99-80%)"
    explanation: Orphanet records urinary sialylated oligosaccharide excretion as very frequent.
  downstream:
  - target: Neuronal lysosomal storage and gliosis
    description: Nervous-system lysosomal storage is associated with glial LAMP1 accumulation, astrogliosis, and the progressive neurologic syndrome.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Lysosomal LAMP1 accumulation and glial activation disrupt neural circuitry and motor function.
    evidence:
    - reference: PMID:38321198
      reference_title: Gene therapy corrects the neurological deficits of mice with sialidosis.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        Untreated Neu1-/- mice showed astrogliosis and microglial LAMP1
        accumulation in the nervous system, including brain, spinal cord, and
        dorsal root ganglion, together with impaired motor function.
      explanation: The Neu1-deficient mouse model links nervous-system lysosomal pathology and gliosis to motor dysfunction.
    - reference: PMID:41665440
      reference_title: "Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "clinically characterized by progressive ataxia, myoclonic seizures (MS),"
      explanation: The clinical review links storage disease to progressive neurologic manifestations.
  - target: Retinal ganglion cell layer storage
    description: Sialyloligosaccharide accumulation in perifoveal ganglion-cell and retinal nerve-fiber layers produces the characteristic retinal pathology.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:32453490
      reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The appearance of macular cherry red spots is caused by the accumulation of sialyloligosaccharides in the perifoveal ganglion cell layer and RNFL."
      explanation: The Type 1 ophthalmic cohort links sialyloligosaccharide storage to retinal ganglion-cell and nerve-fiber-layer pathology.
  - target: Urinary excretion of sialylated oligosaccharides
    description: Systemic sialylated metabolite storage is reflected by increased urinary sialylated oligosaccharide excretion.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:32453490
      reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "urinary excretion of sialylated oligosaccharides"
      explanation: The type 1 cohort review links NEU1 deficiency to urinary sialylated oligosaccharide excretion.
  - target: Increased urinary O-linked sialopeptides
    description: Impaired lysosomal sialylated substrate catabolism produces urinary O-linked sialopeptide accumulation.
    causal_link_type: DIRECT
    evidence:
    - reference: ORPHA:812
      reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "HP:0003461 | Increased urinary O-linked sialopeptides | Very frequent (99-80%)"
      explanation: Orphanet records increased urinary O-linked sialopeptides as a very frequent type 1 storage phenotype.
  - target: Cataract
    description: Accumulated abnormal metabolic products in ocular tissues contribute to punctate cataracts.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Metabolic-product accumulation in the lens alters lens transparency.
    evidence:
    - reference: PMID:32453490
      reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Punctate cataracts were found in all patients"
      explanation: The type 1 cohort documents punctate cataracts in all four patients.
  - target: Corneal opacity
    description: Ocular metabolic-product accumulation can manifest as corneal clouding.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Storage-related abnormal metabolic products affect transparent ocular tissues.
    evidence:
    - reference: PMID:32453490
      reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "punctate cataract and corneal clouding are considered to be characteristic ophthalmic signs"
      explanation: The cohort review identifies corneal clouding as a characteristic ophthalmic sign in sialidosis.
- name: Neuronal lysosomal storage and gliosis
  description: >
    Sialylated storage in the nervous system is associated with glial lysosomal
    pathology and impaired motor function in Neu1-deficient models, while human
    Type 1 disease presents with progressive ataxia, myoclonic seizures, and
    related neurologic manifestations.
  cell_types:
  - preferred_term: Neuron
    term:
      id: CL:0000540
      label: neuron
  - preferred_term: Astrocyte
    term:
      id: CL:0000127
      label: astrocyte
  - preferred_term: Microglial cell
    term:
      id: CL:0000129
      label: microglial cell
  biological_processes:
  - preferred_term: nervous system process
    term:
      id: GO:0050877
      label: nervous system process
    modifier: ABNORMAL
  locations:
  - preferred_term: Brain
    term:
      id: UBERON:0000955
      label: brain
  evidence:
  - reference: PMID:38321198
    reference_title: Gene therapy corrects the neurological deficits of mice with sialidosis.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Untreated Neu1-/- mice showed astrogliosis and microglial"
    explanation: The Neu1-deficient mouse model supports lysosomal neurologic pathology with glial activation.
  - reference: PMID:41665440
    reference_title: "Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "is clinically characterized by progressive ataxia, myoclonic seizures (MS),"
    explanation: The review identifies progressive ataxia and myoclonic seizures as core clinical features.
  downstream:
  - target: Seizure
    description: Progressive neuronal storage and glial pathology cause network dysfunction that manifests as seizures.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Lysosomal neuronal dysfunction and gliosis lower seizure threshold in cortical networks.
    evidence:
    - reference: PMID:32453490
      reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "A total of 75% (3/4) of patients developed seizures and cerebellar ataxia."
      explanation: The type 1 cohort supports seizures as a frequent neurologic manifestation.
  - target: Generalized myoclonic seizure
    description: Neural storage-related cortical hyperexcitability manifests as progressive myoclonic seizures.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Storage-related cortical circuit dysfunction produces progressive myoclonic epilepsy.
    evidence:
    - reference: PMID:41665440
      reference_title: "Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "is clinically characterized by progressive ataxia, myoclonic seizures (MS),"
      explanation: The 2026 review identifies myoclonic seizures as a core type 1 neurologic manifestation.
  - target: Ataxia
    description: Nervous-system storage and gliosis disrupt cerebellar and motor circuitry, causing ataxia.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Cerebellar and motor circuit dysfunction impairs coordination.
    evidence:
    - reference: PMID:32453490
      reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "A total of 75% (3/4) of patients developed seizures and cerebellar ataxia."
      explanation: The type 1 cohort supports cerebellar ataxia as a frequent neurologic manifestation.
  - target: Gait disturbance
    description: Progressive ataxia and motor dysfunction produce gait impairment.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Cerebellar and motor pathway dysfunction impair gait coordination.
    evidence:
    - reference: ORPHA:812
      reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "HP:0001288 | Gait disturbance | Very frequent (99-80%)"
      explanation: Orphanet records gait disturbance as a very frequent type 1 phenotype.
  - target: Decreased nerve conduction velocity
    description: Peripheral nervous system involvement in type 1 can include decreased nerve conduction velocity.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: ORPHA:812
      reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "HP:0000762 | Decreased nerve conduction velocity | Frequent (79-30%)"
      explanation: Orphanet records decreased nerve conduction velocity as a frequent type 1 phenotype.
  - target: Myoclonus
    description: Progressive cortical and motor network dysfunction produces myoclonus.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Storage-related cortical hyperexcitability drives progressive myoclonus.
    evidence:
    - reference: PMID:32453490
      reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "On neurological assessment, 75% (3/4) of patients had a history of progressive myoclonus"
      explanation: The type 1 cohort documents progressive myoclonus in three of four patients.
  - target: Tremor
    description: Motor circuit involvement can manifest as intentional tremor.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Cerebellar and motor pathway dysfunction produce action tremor.
    evidence:
    - reference: PMID:23291686
      reference_title: Clinical and serial MRI findings of a sialidosis type I patient with a novel missense mutation in the NEU1 gene.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "myoclonus, intentional tremors, limb and gait ataxia, hyperreflexia and macular"
      explanation: The type 1 case report documents intentional tremor with other neurologic manifestations.
  - target: Dysarthria
    description: Progressive motor and cerebellar pathway involvement can impair speech articulation.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Cerebellar and bulbar motor pathway dysfunction disrupt speech motor control.
    evidence:
    - reference: PMID:32453490
      reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "evolving to slurred speech and dysphagia in the late stage."
      explanation: The type 1 cohort supports progressive speech involvement in late-stage disease.
  - target: Hyperreflexia
    description: Central motor pathway involvement can manifest as hyperreflexia.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Upper motor pathway dysfunction increases reflex responses.
    evidence:
    - reference: PMID:23291686
      reference_title: Clinical and serial MRI findings of a sialidosis type I patient with a novel missense mutation in the NEU1 gene.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "myoclonus, intentional tremors, limb and gait ataxia, hyperreflexia and macular"
      explanation: The type 1 case report documents hyperreflexia with ataxia and myoclonus.
  - target: EEG abnormality
    description: Epileptic network dysfunction can produce diffuse spike-wave EEG abnormalities.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Cortical hyperexcitability produces epileptiform spike-wave discharges.
    evidence:
    - reference: PMID:32453490
      reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "EEG showed different extents of diffuse paroxysmal features as spike‐wave complexes in two patients."
      explanation: The type 1 cohort documents diffuse paroxysmal EEG abnormalities.
  - target: Cerebellar atrophy
    description: Progressive neural storage disease can be accompanied by cerebellar and brain atrophy.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Chronic storage-related neurodegeneration causes structural brain volume loss in some patients.
    evidence:
    - reference: PMID:23291686
      reference_title: Clinical and serial MRI findings of a sialidosis type I patient with a novel missense mutation in the NEU1 gene.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Serial brain MRI showed diffuse brain atrophy progressing rapidly"
      explanation: Serial MRI in a type 1 patient supports progressive neurodegeneration with brain atrophy.
- name: Retinal ganglion cell layer storage
  description: >
    In Type 1 disease, sialyloligosaccharide and related metabolic-product
    accumulation in the perifoveal ganglion cell layer and retinal nerve fiber
    layer produces OCT/FAF abnormalities and the macular cherry-red spot.
  cell_types:
  - preferred_term: Retinal ganglion cell
    term:
      id: CL:0000740
      label: retinal ganglion cell
  biological_processes:
  - preferred_term: visual perception
    term:
      id: GO:0007601
      label: visual perception
    modifier: ABNORMAL
  locations:
  - preferred_term: Retina
    term:
      id: UBERON:0000966
      label: retina
  evidence:
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The appearance of macular cherry red spots is caused by the accumulation of sialyloligosaccharides in the perifoveal ganglion cell layer and RNFL."
    explanation: The clinical Type 1 cohort explains the retinal storage basis of cherry-red spots.
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Accumulation of metabolic products in the lens, ganglion cell, and RNFL are characteristic ocular findings"
    explanation: The cohort identifies lens, ganglion-cell, and RNFL metabolic-product accumulation as characteristic ocular pathology.
  downstream:
  - target: Retinopathy
    description: Ganglion-cell and retinal nerve fiber layer storage produces retinal OCT abnormalities.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:32453490
      reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "OCT showed increased reflectivity in the retinal nerve fiber layer (RNFL) and ganglion cell layer in all patients."
      explanation: OCT abnormalities in RNFL and ganglion-cell layers support retinopathy downstream of retinal storage.
  - target: Visual impairment
    description: Retinal and visual-pathway storage abnormalities impair visual function.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Retinal nerve fiber layer and ganglion-cell pathology disrupt visual pathway signaling.
    evidence:
    - reference: PMID:32453490
      reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "On ophthalmological assessment, all patients presented with visual impairment."
      explanation: The type 1 cohort documents visual impairment in all four patients.
  - target: Progressive visual loss
    description: Progressive retinal and visual-pathway involvement causes worsening vision.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Ongoing storage pathology in retinal ganglion-cell and nerve-fiber layers disrupts visual function.
    evidence:
    - reference: PMID:32453490
      reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Patients with sialidosis type 1 typically present progressive myoclonus epilepsy (PME) in their second or third decade of life, as well as progressive impaired vision and macular cherry red spots."
      explanation: The cohort review identifies progressive impaired vision as a typical type 1 manifestation.
  - target: Nystagmus
    description: Visual pathway impairment can manifest with nystagmus.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:32453490
      reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Severe nystagmus was found in two patients."
      explanation: The type 1 cohort documents nystagmus in two of four patients.
  - target: Cherry red spot of the macula
    description: Perifoveal ganglion-cell and RNFL storage creates the macular cherry-red spot.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:32453490
      reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The appearance of macular cherry red spots is caused by the accumulation of sialyloligosaccharides in the perifoveal ganglion cell layer and RNFL."
      explanation: The ophthalmic cohort directly explains the storage basis of macular cherry-red spots.
genetic:
- name: Biallelic NEU1 pathogenic variants
  gene_term:
    preferred_term: NEU1
    term:
      id: hgnc:7758
      label: NEU1
  association: Causative
  relationship_type: CAUSATIVE
  features: >
    Biallelic pathogenic variants in NEU1 cause primary lysosomal
    neuraminidase deficiency. Type I disease is associated with residual mild
    alleles or severe-mild variant combinations that retain enough activity to
    produce later-onset, normomorphic disease rather than severe type II disease.
  inheritance:
  - name: Autosomal recessive inheritance
  evidence:
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "NEU1 | neuraminidase 1 | hgnc:7758 | Disease-causing germline mutation(s) in"
    explanation: Orphanet identifies NEU1 as the disease-causing gene for Sialidosis type 1.
  - reference: PMID:28138907
    reference_title: Sialidosis Type 1 with a Novel Mutation in the Neuraminidase-1 (NEU1) Gene.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Genetic analysis identified novel homozygous"
    explanation: The case report identifies a homozygous NEU1 variant in a patient with Sialidosis type 1.
  - reference: PMID:38600684
    reference_title: Clinical and Structural Characteristics of NEU1 Variants Causing Sialidosis Type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "a newly reported family carrying N-acetyl-α-neuraminidase-1"
    explanation: The study reports a family with NEU1 variants causing Sialidosis type 1.
biochemical:
- name: Reduced neuraminidase activity
  presence: Reduced
  context: Diagnostic enzymatic defect
  notes: >
    Reduced lysosomal neuraminidase/sialidase activity is the primary
    biochemical defect in Sialidosis type 1.
  evidence:
  - reference: PMID:28138907
    reference_title: Sialidosis Type 1 with a Novel Mutation in the Neuraminidase-1 (NEU1) Gene.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "deficiency of neuraminidase. Genetic analysis identified novel homozygous"
    explanation: Patient enzyme analysis supports neuraminidase deficiency as the diagnostic defect.
  - reference: PMID:38600684
    reference_title: Clinical and Structural Characteristics of NEU1 Variants Causing Sialidosis Type 1.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "a sialidase activity assay. Cherry-red spots were more prevalent in the"
    explanation: Functional activity testing supports variant-specific sialidase deficiency.
  readouts:
  - target: NEU1 lysosomal neuraminidase deficiency
    relationship: READOUT_OF
    direction: NEGATIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Reduced lysosomal neuraminidase activity is the diagnostic enzymatic readout of deficient NEU1 function.
    evidence:
    - reference: PMID:28138907
      reference_title: Sialidosis Type 1 with a Novel Mutation in the Neuraminidase-1 (NEU1) Gene.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "deficiency of neuraminidase. Genetic analysis identified novel homozygous"
      explanation: Patient enzyme and molecular testing support reduced neuraminidase activity as the biochemical readout of NEU1 deficiency.
- name: Urinary sialylated oligosaccharides
  presence: Elevated
  context: Diagnostic urinary storage biomarker
  notes: >
    Elevated urinary sialylated oligosaccharides reflect impaired degradation of
    sialylated glycoconjugates.
  evidence:
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0012061 | Urinary excretion of sialylated oligosaccharides | Very frequent (99-80%)"
    explanation: Orphanet records urinary sialylated oligosaccharide excretion as very frequent.
  - reference: PMID:32143456
    reference_title: Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "accumulation of sialylated metabolites in tissues and body fluids."
    explanation: The study supports sialylated metabolite accumulation as the biochemical storage signature.
  readouts:
  - target: Sialylated metabolite lysosomal storage
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Elevated urinary sialylated oligosaccharides report systemic accumulation of sialylated storage metabolites.
    evidence:
    - reference: PMID:32453490
      reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "leading to abnormal tissue accumulation as well as urinary excretion of sialylated oligosaccharides"
      explanation: The type 1 cohort review links the storage mechanism to urinary sialylated oligosaccharide excretion.
- name: Urinary O-linked sialopeptides
  presence: Elevated
  context: Diagnostic urinary storage biomarker
  notes: >
    Orphanet lists increased urinary O-linked sialopeptides as a very frequent
    biochemical phenotype.
  evidence:
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003461 | Increased urinary O-linked sialopeptides | Very frequent (99-80%)"
    explanation: Orphanet records this urinary glycopeptide abnormality as very frequent.
  readouts:
  - target: Sialylated metabolite lysosomal storage
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Increased urinary O-linked sialopeptides are a diagnostic readout of sialylated lysosomal storage in Sialidosis type 1.
    evidence:
    - reference: ORPHA:812
      reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "HP:0003461 | Increased urinary O-linked sialopeptides | Very frequent (99-80%)"
      explanation: Orphanet records increased urinary O-linked sialopeptides as a very frequent biochemical manifestation, supporting this urinary marker as a readout of the storage node.
diagnosis:
- name: NEU1 genetic testing
  description: >
    Molecular diagnosis confirms biallelic NEU1 pathogenic variants in a
    compatible clinical and biochemical context.
  diagnosis_term:
    preferred_term: genetic testing
    term:
      id: MAXO:0000127
      label: genetic testing
  results: Biallelic NEU1 pathogenic variants
  evidence:
  - reference: PMID:28138907
    reference_title: Sialidosis Type 1 with a Novel Mutation in the Neuraminidase-1 (NEU1) Gene.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Genetic analysis identified novel homozygous"
    explanation: The case report supports NEU1 molecular testing as confirmatory.
histopathology:
- name: Retinal ganglion cell and nerve fiber layer storage
  finding_term:
    preferred_term: Abnormal cell morphology
    term:
      id: HP:0025461
      label: Abnormal cell morphology
  diagnostic: true
  description: >
    OCT and fundus-autofluorescence findings in Type 1 disease reflect
    storage-related abnormality in the perifoveal ganglion cell layer and
    retinal nerve fiber layer.
  evidence:
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The appearance of macular cherry red spots is caused by the accumulation of sialyloligosaccharides in the perifoveal ganglion cell layer and RNFL."
    explanation: The Type 1 cohort identifies the cellular retinal storage basis of the macular cherry-red spot.
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "OCT showed increased reflectivity in the retinal nerve fiber layer (RNFL) and ganglion cell layer in all patients."
    explanation: OCT evidence supports a microscopic/cellular retinal finding in Type 1 disease.
phenotypes:
- name: Retinopathy
  frequency: VERY_FREQUENT
  diagnostic: true
  phenotype_term:
    preferred_term: Retinopathy
    term:
      id: HP:0000488
      label: Retinopathy
  evidence:
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "OCT showed increased reflectivity in the retinal nerve fiber layer (RNFL) and ganglion cell layer in all patients."
    explanation: The Type 1 ophthalmic cohort supports retinopathy with OCT abnormalities in all patients.
- name: Visual impairment
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Visual impairment
    term:
      id: HP:0000505
      label: Visual impairment
  evidence:
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "On ophthalmological assessment, all patients presented with visual impairment."
    explanation: The Type 1 cohort documents visual impairment in all four patients.
- name: Cataract
  phenotype_term:
    preferred_term: Cataract
    term:
      id: HP:0000518
      label: Cataract
  evidence:
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Punctate cataracts were found in all patients"
    explanation: The Type 1 ophthalmic cohort supports cataract as a recurrent ocular manifestation.
- name: Progressive visual loss
  phenotype_term:
    preferred_term: Progressive visual loss
    term:
      id: HP:0000529
      label: Progressive visual loss
  evidence:
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients with sialidosis type 1 typically present progressive myoclonus epilepsy (PME) in their second or third decade of life, as well as progressive impaired vision and macular cherry red spots."
    explanation: The Type 1 review section identifies progressive impaired vision as a typical manifestation.
- name: Nystagmus
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Nystagmus
    term:
      id: HP:0000639
      label: Nystagmus
  evidence:
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Severe nystagmus was found in two patients."
    explanation: The Type 1 cohort documents nystagmus in two of four patients.
- name: Decreased nerve conduction velocity
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Decreased nerve conduction velocity
    term:
      id: HP:0000762
      label: Decreased nerve conduction velocity
  evidence:
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000762 | Decreased nerve conduction velocity | Frequent (79-30%)"
    explanation: Orphanet provides the disease-phenotype association and frequency band.
- name: Seizure
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Seizure
    term:
      id: HP:0001250
      label: Seizure
  evidence:
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A total of 75% (3/4) of patients developed seizures and cerebellar ataxia."
    explanation: The Type 1 cohort supports seizures in three of four patients.
  - reference: PMID:41665440
    reference_title: "Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "bilateral tonic-clonic seizures (BTCS), and distinctive ophthalmological"
    explanation: The 2026 treatment review identifies myoclonic and bilateral tonic-clonic seizures as core features.
- name: Generalized myoclonic seizure
  frequency: FREQUENT
  diagnostic: true
  phenotype_term:
    preferred_term: Progressive myoclonus epilepsy
    term:
      id: HP:0002123
      label: Generalized myoclonic seizure
  evidence:
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Three out of four patients presented progressive myoclonus epilepsy."
    explanation: The Type 1 cohort supports progressive myoclonus epilepsy in three of four patients.
  - reference: PMID:41665440
    reference_title: "Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "is clinically characterized by progressive ataxia, myoclonic seizures (MS),"
    explanation: The 2026 review identifies myoclonic seizures as a core Type 1 manifestation.
- name: Ataxia
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Ataxia
    term:
      id: HP:0001251
      label: Ataxia
  evidence:
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A total of 75% (3/4) of patients developed seizures and cerebellar ataxia."
    explanation: The Type 1 cohort supports cerebellar ataxia in three of four patients.
  - reference: PMID:28138907
    reference_title: Sialidosis Type 1 with a Novel Mutation in the Neuraminidase-1 (NEU1) Gene.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The patient developed ataxia and myoclonus at 9 y of age."
    explanation: The case report supports ataxia as a Type 1 manifestation.
- name: Gait disturbance
  phenotype_term:
    preferred_term: Gait disturbance
    term:
      id: HP:0001288
      label: Gait disturbance
  evidence:
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001288 | Gait disturbance | Very frequent (99-80%)"
    explanation: Orphanet records gait disturbance for Sialidosis type 1.
  - reference: PMID:23291686
    reference_title: Clinical and serial MRI findings of a sialidosis type I patient with a novel missense mutation in the NEU1 gene.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "myoclonus, intentional tremors, limb and gait ataxia, hyperreflexia and macular"
    explanation: The Type 1 case report supports gait ataxia.
- name: Myoclonus
  frequency: FREQUENT
  diagnostic: true
  phenotype_term:
    preferred_term: Myoclonus
    term:
      id: HP:0001336
      label: Myoclonus
  evidence:
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "On neurological assessment, 75% (3/4) of patients had a history of progressive myoclonus"
    explanation: The Type 1 cohort documents progressive myoclonus in three of four patients.
  - reference: PMID:33121223
    reference_title: "Sialidosis Type I without a Cherry Red Spot- Is There a Genetic Basis?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "sialidosis type I with a typical presentation of progressive cortical myoclonus"
    explanation: Genetically confirmed cases support progressive cortical myoclonus as a typical presentation.
- name: Tremor
  phenotype_term:
    preferred_term: Tremor
    term:
      id: HP:0001337
      label: Tremor
  evidence:
  - reference: PMID:23291686
    reference_title: Clinical and serial MRI findings of a sialidosis type I patient with a novel missense mutation in the NEU1 gene.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "myoclonus, intentional tremors, limb and gait ataxia, hyperreflexia and macular"
    explanation: The Type 1 case report supports intentional tremor.
- name: Dysarthria
  phenotype_term:
    preferred_term: Dysarthria
    term:
      id: HP:0001260
      label: Dysarthria
  evidence:
  - reference: PMID:23291686
    reference_title: Clinical and serial MRI findings of a sialidosis type I patient with a novel missense mutation in the NEU1 gene.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "to our hospital at age 16. On admission, subnormal intelligence, dysarthria,"
    explanation: The Type 1 case report documents dysarthria.
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "evolving to slurred speech and dysphagia in the late stage."
    explanation: The Type 1 cohort supports progressive speech involvement in late-stage disease.
- name: Hyperreflexia
  phenotype_term:
    preferred_term: Hyperreflexia
    term:
      id: HP:0001347
      label: Hyperreflexia
  evidence:
  - reference: PMID:23291686
    reference_title: Clinical and serial MRI findings of a sialidosis type I patient with a novel missense mutation in the NEU1 gene.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "myoclonus, intentional tremors, limb and gait ataxia, hyperreflexia and macular"
    explanation: The Type 1 case report documents hyperreflexia.
- name: EEG abnormality
  frequency: FREQUENT
  phenotype_term:
    preferred_term: EEG abnormality
    term:
      id: HP:0002353
      label: EEG abnormality
  evidence:
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "EEG showed different extents of diffuse paroxysmal features as spike‐wave complexes in two patients."
    explanation: The Type 1 cohort documents EEG abnormalities in two of four patients.
- name: Cerebellar atrophy
  phenotype_term:
    preferred_term: Cerebellar atrophy
    term:
      id: HP:0001272
      label: Cerebellar atrophy
  evidence:
  - reference: PMID:10686466
    reference_title: "Type I sialidosis: a clinical, biochemical and neuroradiological study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "showed severe atrophy of the cerebellum and pontine region"
    explanation: The Type I study documents cerebellar atrophy.
  - reference: PMID:23291686
    reference_title: Clinical and serial MRI findings of a sialidosis type I patient with a novel missense mutation in the NEU1 gene.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Serial brain MRI showed diffuse brain atrophy progressing rapidly"
    explanation: Serial imaging supports progressive neurodegeneration in some Type I patients.
- name: Increased urinary O-linked sialopeptides
  frequency: VERY_FREQUENT
  diagnostic: true
  phenotype_term:
    preferred_term: Increased urinary O-linked sialopeptides
    term:
      id: HP:0003461
      label: Increased urinary O-linked sialopeptides
  evidence:
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003461 | Increased urinary O-linked sialopeptides | Very frequent (99-80%)"
    explanation: Orphanet records increased urinary O-linked sialopeptides for Sialidosis type 1.
- name: Corneal opacity
  phenotype_term:
    preferred_term: Corneal opacity
    term:
      id: HP:0007957
      label: Corneal opacity
  evidence:
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "punctate cataract and corneal clouding are considered to be characteristic ophthalmic signs"
    explanation: The Type 1 ophthalmic cohort review supports corneal clouding as an ophthalmic sign.
- name: Cherry red spot of the macula
  frequency: FREQUENT
  diagnostic: true
  phenotype_term:
    preferred_term: Cherry red spot of the macula
    term:
      id: HP:0010729
      label: Cherry red spot of the macula
  evidence:
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Macular cherry red spots are a distinctive feature of the ocular manifestation of sialidosis type 1."
    explanation: The Type 1 ophthalmic cohort identifies cherry-red spots as a distinctive ocular feature.
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "According to the 45 genetically confirmed sialidosis type 1 cases, macular cherry red spots were observed in only 51.2% (22/43) of the patients"
    explanation: The literature review within the cohort supports a frequent, not universal, frequency estimate.
- name: Urinary excretion of sialylated oligosaccharides
  frequency: VERY_FREQUENT
  diagnostic: true
  phenotype_term:
    preferred_term: Urinary excretion of sialylated oligosaccharides
    term:
      id: HP:0012061
      label: Urinary excretion of sialylated oligosaccharides
  evidence:
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0012061 | Urinary excretion of sialylated oligosaccharides | Very frequent (99-80%)"
    explanation: Orphanet records urinary sialylated oligosaccharide excretion as very frequent.
  - reference: PMID:32453490
    reference_title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "urinary excretion of sialylated oligosaccharides"
    explanation: The Type 1 cohort review links NEU1 deficiency to urinary sialylated oligosaccharide excretion.
treatments:
- name: Antiseizure pharmacotherapy for myoclonic and bilateral tonic-clonic seizures
  description: >
    Symptomatic antiseizure treatment may reduce myoclonic seizures and
    bilateral tonic-clonic seizures, although data remain too limited for
    standardized guidelines.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: acetazolamide
      term:
        id: CHEBI:27690
        label: acetazolamide
    - preferred_term: perampanel
      term:
        id: CHEBI:71013
        label: perampanel
    - preferred_term: levetiracetam
      term:
        id: CHEBI:6437
        label: levetiracetam
    - preferred_term: valproate
      term:
        id: CHEBI:60654
        label: valproate
    - preferred_term: clonazepam
      term:
        id: CHEBI:3756
        label: clonazepam
    - preferred_term: zonisamide
      term:
        id: CHEBI:10127
        label: zonisamide
  target_phenotypes:
  - preferred_term: Seizure
    term:
      id: HP:0001250
      label: Seizure
  - preferred_term: Myoclonus
    term:
      id: HP:0001336
      label: Myoclonus
  evidence:
  - reference: PMID:41665440
    reference_title: "Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "CZP, and ZNS, demonstrated fairly consistent efficacy in managing MS and BTCS."
    explanation: The 2026 multicenter analysis reports fairly consistent seizure-management efficacy for several antiseizure medications.
  - reference: PMID:41665440
    reference_title: "Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "define standardized treatment guidelines, some ASMs, such as ACZ, PER, LEV, VPA,"
    explanation: The review limits the strength of treatment recommendations despite symptomatic benefit.
- name: Sodium oxybate for refractory myoclonic seizures
  description: >
    Sodium oxybate may be considered for refractory disabling myoclonic seizures
    in selected Sialidosis type 1 cases, but the evidence remains limited and
    non-standardized.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: Sodium Oxybate
      term:
        id: NCIT:C61870
        label: Sodium Oxybate
  target_phenotypes:
  - preferred_term: Generalized myoclonic seizure
    term:
      id: HP:0002123
      label: Generalized myoclonic seizure
  - preferred_term: Myoclonus
    term:
      id: HP:0001336
      label: Myoclonus
  evidence:
  - reference: PMID:41665440
    reference_title: "Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Sodium oxybate or deep-brain stimulation may be considered in refractory cases."
    explanation: The multicenter review lists sodium oxybate as a consideration for refractory cases, without establishing standardized efficacy.
- name: Deep-brain stimulation for refractory myoclonic seizures
  description: >
    Deep-brain stimulation is a refractory-case option mentioned in the 2026
    treatment review; it is not established as routine therapy for Sialidosis
    type 1.
  treatment_term:
    preferred_term: deep brain stimulation
    term:
      id: MAXO:0000943
      label: deep brain stimulation
  target_phenotypes:
  - preferred_term: Generalized myoclonic seizure
    term:
      id: HP:0002123
      label: Generalized myoclonic seizure
  - preferred_term: Myoclonus
    term:
      id: HP:0001336
      label: Myoclonus
  evidence:
  - reference: PMID:41665440
    reference_title: "Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Sodium oxybate or deep-brain stimulation may be considered in refractory cases."
    explanation: The multicenter review lists deep-brain stimulation as a consideration for refractory cases, without establishing standardized efficacy.
- name: Supportive multidisciplinary care
  description: >
    Supportive management addresses progressive movement impairment, visual
    impairment, seizures, rehabilitation needs, and developmental or educational
    support in the absence of an approved curative therapy.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  target_phenotypes:
  - preferred_term: Ataxia
    term:
      id: HP:0001251
      label: Ataxia
  - preferred_term: Progressive visual loss
    term:
      id: HP:0000529
      label: Progressive visual loss
  evidence:
  - reference: PMID:41665440
    reference_title: "Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Given the lack of curative options, in this study, we investigated"
    explanation: The review supports symptomatic management in the absence of curative options.
  - reference: PMID:32143456
    reference_title: Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "for which no therapy is currently available."
    explanation: The therapy study supports the absence of an established disease-modifying therapy.
- name: Investigational betaine and PPCA-based therapeutic strategies
  description: >
    Preclinical and patient-fibroblast experiments suggest that PPCA-based
    chaperone approaches and selected dietary or pharmacologic compounds,
    including betaine, can increase residual mutant NEU1 activity, but these
    remain investigational.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: glycine betaine
      term:
        id: CHEBI:17750
        label: glycine betaine
  target_mechanisms:
  - target: NEU1 lysosomal neuraminidase deficiency
    treatment_effect: RESTORES
    description: PPCA and selected compounds are intended to increase residual mutant NEU1 activity.
    evidence:
    - reference: PMID:32143456
      reference_title: Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I.
      supports: PARTIAL
      evidence_source: IN_VITRO
      snippet: "primary fibroblasts. We observed a small, but consistent increase in NEU1"
      explanation: Patient fibroblast experiments support partial restoration of residual NEU1 activity.
  evidence:
  - reference: PMID:32143456
    reference_title: Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I.
    supports: PARTIAL
    evidence_source: MODEL_ORGANISM
    snippet: "increased the levels of mutant NEU1 and resolved the"
    explanation: Mouse-model data suggest betaine can improve mutant NEU1 levels and oligosacchariduria, but this remains preclinical.
- name: Investigational AAV9 NEU1 and CTSA gene therapy
  description: >
    AAV-mediated coexpression of NEU1 and CTSA/PPCA is a preclinical strategy
    intended to restore lysosomal NEU1 activity and reduce neurologic pathology;
    current support comes from mouse studies rather than human trials.
  treatment_term:
    preferred_term: gene therapy
    term:
      id: MAXO:0001001
      label: gene therapy
  target_mechanisms:
  - target: NEU1 lysosomal neuraminidase deficiency
    treatment_effect: RESTORES
    description: AAV9-P3-NP delivers NEU1 and CTSA cDNAs to restore lysosomal NEU1 function.
    evidence:
    - reference: PMID:38321198
      reference_title: Gene therapy corrects the neurological deficits of mice with sialidosis.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: "The vector, AAV9-P3-NP, included the human NEU1 promoter, NEU1 cDNA,"
      explanation: The mouse study describes the NEU1/CTSA AAV vector design.
  evidence:
  - reference: PMID:38321198
    reference_title: Gene therapy corrects the neurological deficits of mice with sialidosis.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "decreased astrogliosis and LAMP1 accumulation in the nervous system"
    explanation: The Neu1 knockout mouse study supports neurologic-pathology improvement after AAV treatment.
- name: Hematopoietic cell transplantation
  description: >
    Hematopoietic cell transplantation has been reported in one adolescent with
    Sialidosis type 1. Biomarkers improved after engraftment, but motor decline
    continued, so this remains a highly selected and uncertain intervention.
  treatment_term:
    preferred_term: hematopoietic stem cell transplantation
    term:
      id: MAXO:0000747
      label: hematopoietic stem cell transplantation
  target_mechanisms:
  - target: Sialylated metabolite lysosomal storage
    treatment_effect: MODULATES
    description: Donor engraftment was associated with plasma and urine biomarker response.
    evidence:
    - reference: PMID:35242566
      reference_title: Hematopoietic cell transplantation for sialidosis type I.
      supports: PARTIAL
      evidence_source: HUMAN_CLINICAL
      snippet: "plasma and urine biomarkers responded concurrently with engraftment."
      explanation: The single case report supports biomarker response after BMT.
  evidence:
  - reference: PMID:35242566
    reference_title: Hematopoietic cell transplantation for sialidosis type I.
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "overall decline in motor performance."
    explanation: The same case report limits evidence strength because neurologic motor performance still declined.
- name: Genetic counseling
  description: >
    Genetic counseling supports recurrence-risk assessment and family planning
    for autosomal recessive NEU1-associated disease.
  treatment_term:
    preferred_term: genetic counseling
    term:
      id: MAXO:0000079
      label: genetic counseling
  evidence:
  - reference: ORPHA:812
    reference_title: "Sialidosis type 1 (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Autosomal recessive"
    explanation: Autosomal recessive inheritance supports genetic counseling for recurrence risk.
references:
- reference: ORPHA:812
  title: Sialidosis type 1
  found_in:
  - Sialidosis_Type_1-deep-research-fallback.md
- reference: PMID:10686466
  title: "Type I sialidosis: a clinical, biochemical and neuroradiological study."
  found_in:
  - Sialidosis_Type_1-deep-research-fallback.md
- reference: PMID:10944856
  title: Molecular and structural studies of Japanese patients with sialidosis type 1.
  found_in:
  - Sialidosis_Type_1-deep-research-fallback.md
- reference: PMID:23291686
  title: Clinical and serial MRI findings of a sialidosis type I patient with a novel missense mutation in the NEU1 gene.
  found_in:
  - Sialidosis_Type_1-deep-research-fallback.md
- reference: PMID:28138907
  title: Sialidosis Type 1 with a Novel Mutation in the Neuraminidase-1 (NEU1) Gene.
  found_in:
  - Sialidosis_Type_1-deep-research-fallback.md
- reference: PMID:32143456
  title: Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I.
  found_in:
  - Sialidosis_Type_1-deep-research-fallback.md
- reference: PMID:32453490
  title: Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
  found_in:
  - Sialidosis_Type_1-deep-research-fallback.md
- reference: PMID:33121223
  title: "Sialidosis Type I without a Cherry Red Spot- Is There a Genetic Basis?"
  found_in:
  - Sialidosis_Type_1-deep-research-fallback.md
- reference: PMID:35242566
  title: Hematopoietic cell transplantation for sialidosis type I.
  found_in:
  - Sialidosis_Type_1-deep-research-fallback.md
- reference: PMID:38321198
  title: Gene therapy corrects the neurological deficits of mice with sialidosis.
  found_in:
  - Sialidosis_Type_1-deep-research-fallback.md
- reference: PMID:38600684
  title: Clinical and Structural Characteristics of NEU1 Variants Causing Sialidosis Type 1.
  found_in:
  - Sialidosis_Type_1-deep-research-fallback.md
- reference: PMID:41665440
  title: "Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature."
  found_in:
  - Sialidosis_Type_1-deep-research-fallback.md
📚

References & Deep Research

References

12
ORPHA:812
Sialidosis type 1
No top-level findings curated for this source.
PMID:10686466
Type I sialidosis: a clinical, biochemical and neuroradiological study.
No top-level findings curated for this source.
PMID:10944856
Molecular and structural studies of Japanese patients with sialidosis type 1.
No top-level findings curated for this source.
PMID:23291686
Clinical and serial MRI findings of a sialidosis type I patient with a novel missense mutation in the NEU1 gene.
No top-level findings curated for this source.
PMID:28138907
Sialidosis Type 1 with a Novel Mutation in the Neuraminidase-1 (NEU1) Gene.
No top-level findings curated for this source.
PMID:32143456
Conventional and Unconventional Therapeutic Strategies for Sialidosis Type I.
No top-level findings curated for this source.
PMID:32453490
Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1.
No top-level findings curated for this source.
PMID:33121223
Sialidosis Type I without a Cherry Red Spot- Is There a Genetic Basis?
No top-level findings curated for this source.
PMID:35242566
Hematopoietic cell transplantation for sialidosis type I.
No top-level findings curated for this source.
PMID:38321198
Gene therapy corrects the neurological deficits of mice with sialidosis.
No top-level findings curated for this source.
PMID:38600684
Clinical and Structural Characteristics of NEU1 Variants Causing Sialidosis Type 1.
No top-level findings curated for this source.
PMID:41665440
Sialidosis type I: How to alleviate disabling myoclonic seizures?-A multicenter analysis of eight cases and review of the literature.
No top-level findings curated for this source.

Deep Research

1
Fallback ▸
Sialidosis type 1 Deep Research Fallback
none 12 citations 2026-05-04T19:12:00Z

Sialidosis type 1 Deep Research Fallback

Provider Attempts

  • Falcon: just research-disorder falcon Sialidosis_Type_1 initially failed before YAML creation because the disorder file did not exist. After the YAML was created, Falcon started and produced no output beyond startup for several minutes; the provider process was terminated to avoid a long silent deep-research wait.
  • OpenAI: just research-disorder openai Sialidosis_Type_1 was attempted after Falcon and produced no output during bounded wait intervals; the provider process was terminated.

Evidence Scope

The YAML curation integrates deterministic Orphanet structured data and fetched PubMed abstracts:

  • ORPHA:812 provides the direct MONDO:0019346 mapping, OMIM cross-reference, definition, autosomal recessive inheritance, epidemiology, NEU1 disease-causing gene row, natural-history onset, and complete HPO phenotype table.
  • PMID:41665440 provides the current 2026 multicenter clinical review of Sialidosis type I myoclonic seizures, treatment-response evidence for antiseizure medications, and the literature window through September 2025.
  • PMID:38600684 supports the type I genotype-structure-phenotype model in which type I has at least one catalytically active mild NEU1 variant.
  • PMID:32143456 supports the lysosomal NEU1 deficiency mechanism, sialylated metabolite accumulation, patient-fibroblast therapeutic testing, and preclinical betaine findings.
  • PMID:32453490 supports the Type 1/Type 2 clinical distinction, Type 1 neuro-ophthalmic phenotype selection, retinal ganglion-cell/RNFL storage pathology, and the decision not to retain unsupported dysmorphic or skeletal Type 2 features.
  • PMID:28138907, PMID:33121223, PMID:10686466, and PMID:23291686 support human clinical manifestations including ataxia, myoclonus, cherry-red spots, neuraminidase deficiency, and progressive neuroimaging changes.
  • PMID:10944856 supports residual enzyme activity and abnormal trafficking of type I NEU1 variants in molecular studies.
  • PMID:35242566 supports the single reported hematopoietic cell transplantation experience in Sialidosis type I.
  • PMID:38321198 supports investigational AAV-mediated NEU1/CTSA gene therapy in a Neu1 knockout mouse model.

Integration Notes

The curated YAML represents the disease as NEU1-related lysosomal neuraminidase deficiency leading to impaired sialylated glycoconjugate degradation, sialylated metabolite storage, and separate neurologic and retinal Type 1 mechanisms. ORPHA:812 phenotype rows were reconciled against primary Type 1 literature; dysmorphic, skeletal, visceral, and cutaneous rows consistent with Type 2 contamination were not retained without direct Type 1 support. Treatment sections include evidence-backed symptomatic antiseizure pharmacotherapy, refractory-case sodium oxybate and deep-brain stimulation considerations from the 2026 review, supportive care, investigational betaine/PPCA and AAV approaches, hematopoietic cell transplantation with partial evidence, and genetic counseling.