| Phenotype (plain language) | Suggested HPO term(s) | Typical onset/subtype | Frequency / statistics if available | Progression notes | Key source (PMID if known, else DOI) | Evidence citation ids |
|---|---|---|---|---|---|---|
| Developmental plateau/regression and loss of acquired milestones | HP:0002376 Developmental regression; HP:0012758 Neurodevelopmental delay | Late-infantile typically after normal early milestones to ~12 months; juvenile often after initially normal development at 3–5 years | Late-infantile patients “usually exhibited delay or non-acquisition of major milestones”; juvenile patients “usually attained these milestones on time” before later decline | Progressive; late-infantile loses skills earlier and faster, juvenile shows slower decline | D’Souza et al., 2024, DOI:10.1016/j.gim.2024.101144; Ferreira et al., 2020, DOI:10.1016/j.bone.2019.115142 | (pqac-00000009, pqac-00000012) |
| Impaired walking / loss of ambulation | HP:0002355 Difficulty walking; HP:0002505 Ataxia; HP:0001288 Gait disturbance | Late-infantile: 12–18 months onward; juvenile: often first recognized at 3–5 years | Late-infantile: by age 2 most are non-ambulatory; juvenile: many remain ambulatory for years but most are wheelchair-bound by mid-teens | Worsens over time; within-person mobility decline documented longitudinally | Ferreira et al., 2020, DOI:10.1016/j.bone.2019.115142; D’Souza et al., 2024, DOI:10.1016/j.gim.2024.101144 | (pqac-00000012, pqac-00000014) |
| Ataxia / coordination problems | HP:0001251 Ataxia | Common presenting feature, especially juvenile/type 2b | No cohort percentage reported in extracted text; repeatedly described as an early manifestation | Progressive and often followed by dystonia/spasticity | Karimzadeh et al., 2017, DOI:10.1186/s12881-017-0417-4; D’Souza et al., 2024, DOI:10.1016/j.gim.2024.101144 | (pqac-00000003, pqac-00000010) |
| Dystonia / abnormal movements | HP:0001332 Dystonia | More typical in juvenile and later type II course, but can occur in both late-infantile and juvenile | No cohort percentage reported in extracted text | Progressive movement disorder; often follows gait/ataxia symptoms | Karimzadeh et al., 2017, DOI:10.1186/s12881-017-0417-4; Arash-Kaps et al., 2019, DOI:10.1016/j.jpeds.2019.08.016 | (pqac-00000003, pqac-00000002) |
| Spasticity / hyperreflexia | HP:0001257 Spasticity; HP:0001347 Hyperreflexia | Variable, often later in type II | No percentage in extracted text | Progressive upper motor neuron features in a subset | Rha et al., 2021, DOI:10.2147/TACG.S206076 | (pqac-00000001) |
| Speech disorder / dysarthria / loss of speech | HP:0001260 Dysarthria; HP:0002167 Delayed speech and language development; HP:0001344 Progressive neurologic deterioration | Late-infantile: limited expressive language and progressive anarthria; juvenile: often normal speech first, early “stuttering” then dysarthria | Juvenile speech scores decline with age (rho = -0.60); language rho = -0.53 | Progressive communication loss, more severe/earlier in late-infantile | Ferreira et al., 2020, DOI:10.1016/j.bone.2019.115142; D’Souza et al., 2024, DOI:10.1016/j.gim.2024.101144 | (pqac-00000012, pqac-00000011) |
| Swallowing difficulty / dysphagia | HP:0002015 Dysphagia | Seen in both; often clinically important in later childhood | VFSS performed in 82% late-infantile (14/17) and 96% juvenile (23/24); juvenile dietary restriction score worsened with age (rho = -0.68) | Generally progressive feeding/swallow impairment; aspiration risk variable | D’Souza et al., 2024, DOI:10.1016/j.gim.2024.101144 | (pqac-00000009, pqac-00000014) |
| Seizures / epileptiform EEG abnormalities | HP:0001250 Seizure; HP:0002353 EEG abnormality | Variable; can emerge during childhood in both subtypes | At enrollment, seizure treatment in 65% (11/17) late-infantile and 29% (7/24) juvenile; epileptiform EEG activity in 40% (4/10) of abnormal late-infantile EEGs | Progressive neurologic disease; EEG abnormalities common, especially late-infantile | D’Souza et al., 2024, DOI:10.1016/j.gim.2024.101144 | (pqac-00000011, pqac-00000015) |
| Cerebral and cerebellar atrophy on MRI | HP:0002059 Cerebral atrophy; HP:0001272 Cerebellar atrophy | Both subtypes, more severe/rapid in late-infantile | Late-infantile: cerebellar atrophy 11/14 (79%), cerebral cortical atrophy 11/14 (79%); juvenile: cerebral cortical atrophy 17/21 (81%), cerebellar atrophy 6/21 (29%) | Progressive; serial MRI shows faster progression in late-infantile | D’Souza et al., 2024, DOI:10.1016/j.gim.2024.101144 | (pqac-00000011, pqac-00000013) |
| White matter / myelination abnormalities | HP:0002500 Abnormal cerebral white matter morphology; HP:0012447 Delayed myelination | Both; especially notable in late-infantile | Late-infantile: all 8 assessed for myelination abnormal; juvenile white matter injury 13/19 (68%) | Progressive imaging abnormality; used as a biomarker in natural history and trials | D’Souza et al., 2024, DOI:10.1016/j.gim.2024.101144 | (pqac-00000011) |
| Visual impairment with strabismus / nystagmus | HP:0000505 Visual impairment; HP:0000486 Strabismus; HP:0000639 Nystagmus | More severe in late-infantile; can occur in juvenile | Late-infantile: strabismus 17/17 (100%), nystagmus 9/17 (53%), cortical visual impairment 12/17 (71%); juvenile average visual acuity better and less cortical visual impairment | Progressive visual dysfunction; unlike type I, cherry-red spots typically absent | D’Souza et al., 2024, DOI:10.1016/j.gim.2024.101144; Rha et al., 2021, DOI:10.2147/TACG.S206076 | (pqac-00000009, pqac-00000001) |
| Hearing usually normal or near-normal | HP:0000365 Hearing impairment (typically absent); HP:0010788 Abnormal auditory brainstem response | Both subtypes | Peripheral hearing normal in 88% (15/17) late-infantile and 92% (22/24) juvenile; ABR normal in 53% late-infantile and 64% juvenile | Auditory phenotype relatively preserved versus infantile GM1, though ABR abnormalities may occur | D’Souza et al., 2024, DOI:10.1016/j.gim.2024.101144 | (pqac-00000009, pqac-00000014) |
| Skeletal dysplasia / low bone mineral density / odontoid hypoplasia | HP:0002652 Skeletal dysplasia; HP:0000939 Osteopenia; HP:0003307 Odontoid hypoplasia; HP:0100923 Avascular necrosis of the femoral head | Both; odontoid hypoplasia especially late-infantile, hip AVN in some juvenile patients | Lumbar spine, femoral neck, total hip BMD Z-scores about -2.1, -2.2, -1.8; all late-infantile patients had odontoid hypoplasia in the cited cohort | Chronic orthopedic burden; contributes to disability and wheelchair dependence | Ferreira et al., 2020, DOI:10.1016/j.bone.2019.115142 | (pqac-00000012) |
| Cardiac valvular thickening/regurgitation | HP:0001654 Cardiac valvular defect; HP:0001644 Dilated ascending aorta not established here; HP:0006682 Mitral regurgitation; HP:0001653 Aortic regurgitation | More often older juvenile patients | Juvenile ECHO abnormalities in 3/13 with aortic leaflet thickening/regurgitation; one late-infantile patient had mitral valve prolapse | Appears later and is not universal | D’Souza et al., 2024, DOI:10.1016/j.gim.2024.101144 | (pqac-00000013, pqac-00000014) |
| Low β-galactosidase activity (laboratory abnormality) | HP:0012379 Abnormal enzyme/coenzyme activity (suggested broad term) | Present in both subtypes from diagnosis | Serum β-gal 0–5% of pediatric controls (median 0.028); CSF 2–8% (median 0.05) of controls | Stable underlying biochemical defect; central to diagnosis and trial pharmacodynamics | D’Souza et al., 2024, DOI:10.1016/j.gim.2024.101144 | (pqac-00000014) |
| Elevated AST / mild liver chemistry abnormality | HP:0031964 Elevated circulating aspartate aminotransferase concentration | Both, more common in late-infantile | AST elevated in 76% late-infantile and 29% juvenile | Usually mild; part of multisystem monitoring rather than dominant clinical phenotype | D’Souza et al., 2024, DOI:10.1016/j.gim.2024.101144 | (pqac-00000014) |


*Table: This table summarizes the main clinical, imaging, and laboratory phenotypes reported for GM1 gangliosidosis type II, split where possible between late-infantile and juvenile presentations. It is useful for mapping disease features to HPO terms and for distinguishing common progression patterns and frequencies from recent natural-history studies.*