| Disorder (key synonyms) | Causal gene(s) and enzyme/protein | Inheritance | Key stored substrate / biomarker | Core phenotypes (1 line) | Diagnostics (1 line) | Disease-modifying treatments (approved/experimental) | Suggested ontology terms |
|---|---|---|---|---|---|---|---|
| Aspartylglucosaminuria (AGU; aspartylglycosaminuria) | **AGA**; aspartylglucosaminidase / glycosylasparaginase | AR | Aspartylglucosamine and other **glycoasparagines** in urine; aberrant urinary oligosaccharides (pqac-00000067, pqac-00000068, pqac-00000069) | Developmental delay from ~12–15 months, later regression, ID, epilepsy, coarse facies, recurrent diarrhea/infections, MRI abnormalities (pqac-00000067, pqac-00000068, pqac-00000069) | Trio-WES or other molecular testing for **AGA** plus urine UHPLC/HRAM mass spectrometry oligosaccharide profiling (pqac-00000067, pqac-00000069) | No approved disease-modifying therapy identified here; **intrathecal scAAV9/AGA gene therapy** trial planned (NCT07530796); pharmacologic chaperone/betaine reported in later prepublication evidence (pqac-00000059) | MONDO: n/a; HPO: HP:0001249, HP:0001250, HP:0001263; GO BP/CC: glycoprotein catabolic process, lysosome; CL: neuron, oligodendrocyte; UBERON: brain; MAXO: gene therapy, urine metabolite measurement |
| Fucosidosis (historically mucopolysaccharidosis F) | **FUCA1**; α-L-fucosidase | AR | Fucose-containing glycoproteins/glycolipids/oligosaccharides; absent or very low α-L-fucosidase activity; urinary fucose-rich glycoconjugates/glycopeptides (pqac-00000028, pqac-00000029, pqac-00000031, pqac-00000034) | Infantile/childhood psychomotor regression, seizures, spasticity/hypotonia, coarse facies, angiokeratoma/telangiectasia, hepatosplenomegaly, dysostosis multiplex, recurrent infections (pqac-00000028, pqac-00000029, pqac-00000030, pqac-00000032) | Enzyme assay in leukocytes/fibroblasts/plasma, urinary oligosaccharide/glycopeptide studies, confirmatory **FUCA1** sequencing; MRI may show hypomyelination/basal ganglia signal change (pqac-00000028, pqac-00000030, pqac-00000035) | No definitive approved therapy identified; supportive care standard; **HSCT/HCT**, gene therapy and ERT remain investigational or limited-case approaches (pqac-00000032, pqac-00000034) | MONDO: n/a; HPO: HP:0002376, HP:0001250, HP:0000953, HP:0001433; GO BP/CC: fucose-containing compound catabolic process, lysosome; CL: neuron, microglial cell; UBERON: brain, liver, spleen; MAXO: hematopoietic stem cell transplantation, seizure management |
| Alpha-mannosidosis (α-mannosidosis) | **MAN2B1**; lysosomal acid α-mannosidase | AR | Mannose-rich oligosaccharides in serum/urine; low leukocyte α-mannosidase activity (~5–15% or less of normal in reports) (pqac-00000012, pqac-00000015, pqac-00000019) | Hearing loss, recurrent infections/immunodeficiency, skeletal/facial abnormalities, ataxia, hypotonia, developmental delay/ID, psychiatric features; variable severity (pqac-00000012, pqac-00000015, pqac-00000016, pqac-00000019) | Enzyme assay plus **MAN2B1** molecular testing; urinary mannose-rich oligosaccharides as screen; functional monitoring includes 6MWT/3MSCT, hearing, imaging (pqac-00000012, pqac-00000015, pqac-00000017, pqac-00000019) | **Velmanase alfa** approved for non-CNS manifestations (EU 2018; US 2023 in cited evidence); **HSCT** used in selected severe cases; expanded access/real-world pediatric studies ongoing (pqac-00000013, pqac-00000017, pqac-00000060, pqac-00000062, pqac-00000064, pqac-00000065) | MONDO: n/a; HPO: HP:0000365, HP:0002719, HP:0001251, HP:0001252; GO BP/CC: N-glycan catabolic process, lysosome; CL: neuron, immune cell; UBERON: ear, skeleton, brain; MAXO: enzyme replacement therapy, HSCT |
| Sialidosis type I (cherry-red spot myoclonus syndrome; neuraminidase deficiency type I) | **NEU1**; neuraminidase-1 / lysosomal sialidase | AR | Accumulation of sialylated compounds; reduced leukocyte/fibroblast NEU1 activity; urinary sialic acid may be increased but can be variable (pqac-00000020, pqac-00000022, pqac-00000027) | Usually adolescent/young-adult onset progressive myoclonus, ataxia, seizures, visual impairment, bilateral macular cherry-red spots; pooled frequencies: muscle spasms 91.5%, ataxia 75%, seizures 63.6% (pqac-00000024, pqac-00000025, pqac-00000072, pqac-00000073) | **NEU1** sequencing with enzyme assay, ophthalmic exam/OCT, EEG, VEP/SEP, brain MRI; mean onset ~15.7 y and diagnosis ~24.1 y in pooled review (pqac-00000020, pqac-00000024, pqac-00000025, pqac-00000072) | No approved disease-modifying therapy identified here; supportive antiseizure care standard; **AAV-mediated gene therapy** is preclinical/experimental and natural-history study is recruiting (pqac-00000027, pqac-00000052) | MONDO: n/a; HPO: HP:0001336, HP:0001250, HP:0002066, HP:0012047; GO BP/CC: sialylated glycoprotein catabolic process, lysosomal lumen; CL: neuron, retinal cell; UBERON: cerebellum, retina; MAXO: antiseizure medication, genetic testing |
| Galactosialidosis (GS; protective protein/cathepsin A deficiency) | **CTSA**; protective protein/cathepsin A (PPCA), with secondary NEU1 and β-galactosidase deficiency | AR | Sialyloligosaccharides and glycopeptides; absent/undetectable PPCA activity; secondary neuraminidase deficiency (pqac-00000008, pqac-00000006) | Variable infantile/late-infantile/juvenile-adult disease with developmental delay, coarse facies, cherry-red macula, visceromegaly, skeletal deformity, cardiac disease, hearing loss; T-cell defects reported in a family (pqac-00000008, pqac-00000006) | Lysosomal enzyme assays showing PPCA deficiency with confirmatory **CTSA** sequencing; ophthalmic and multisystem assessment (pqac-00000006, pqac-00000008) | No approved disease-modifying therapy identified in retrieved evidence; supportive multidisciplinary care standard; preclinical ERT/chaperone/gene therapy discussed in reviews (pqac-00000008) | MONDO: n/a; HPO: HP:0001249, HP:0001083, HP:0001433, HP:0002650; GO BP/CC: lysosomal multienzyme complex assembly, lysosome; CL: neuron, T cell; UBERON: eye, liver, spleen, heart; MAXO: supportive care, enzyme assay |
| Mucolipidosis II/III (ML II/I-cell disease; ML III alpha/beta; ML III gamma; pseudo-Hurler polydystrophy) | **GNPTAB** (ML II, ML III α/β); **GNPTG** (ML III γ); UDP-GlcNAc:lysosomal-enzyme N-acetylglucosamine-1-phosphotransferase subunits | AR | Defective mannose-6-phosphate tagging; elevated extracellular/plasma lysosomal enzymes (e.g., hexosaminidase, arylsulfatase A, α-L-fucosidase, α-D-mannosidase); urine GAGs often normal (pqac-00000037, pqac-00000038, pqac-00000041, pqac-00000043) | ML II: neonatal/infantile severe skeletal disease, coarse facies, gingival hypertrophy, contractures, cardiopulmonary disease, hepatosplenomegaly, developmental delay, poor survival; ML III: later-onset milder skeletal/joint disease with survival into adulthood/mid-adulthood (pqac-00000036, pqac-00000037, pqac-00000039, pqac-00000040, pqac-00000042, pqac-00000043) | Molecular testing (**GNPTAB/GNPTG**) plus characteristic enzyme pattern in plasma/DBS/fibroblasts; skeletal radiographs and multisystem evaluation; DBS may support minimally invasive screening (pqac-00000036, pqac-00000037, pqac-00000038, pqac-00000041) | No approved disease-modifying therapy identified in current evidence; supportive care standard; experimental biomarker and model-system work ongoing (pqac-00000041, pqac-00000042, pqac-00000043) | MONDO: n/a; HPO: HP:0002758, HP:0001387, HP:0000175, HP:0001638; GO BP/CC: lysosomal enzyme targeting, mannose-6-phosphate biosynthetic process, Golgi/lysosome; CL: chondrocyte, fibroblast; UBERON: skeleton, heart, lung; MAXO: supportive orthopedic/cardiac care, dried blood spot screening |


*Table: This table summarizes the main glycoprotein storage diseases discussed in the evidence base, aligning subtype names, causal genes, biomarkers, phenotypes, diagnostics, treatments, and concise ontology suggestions. It is useful as a compact disease-knowledge-base scaffold for comparing the major glycoproteinoses/oligosaccharidoses.*