| Disease label used in papers | Causal gene | Inheritance | Key distinguishing clinical features | Key diagnostic tests/findings | Typical treatment response notes | Key recent references |
|---|---|---|---|---|---|---|
| Dopamine transporter deficiency syndrome (DTDS); infantile parkinsonism-dystonia | **SLC6A3** | Usually autosomal recessive due to biallelic loss-of-function variants; review also notes heterozygous dominant-negative **SLC6A3** variants in atypical DTDS (pqac-00000019, pqac-00000003) | Infantile onset, often within first 6 months; irritability, feeding difficulties, hypotonia, delayed motor milestones; hyperkinetic movements (chorea, dystonia, ballismus, orolingual dyskinesia) progressing to parkinsonism-dystonia with bradykinesia, tremor, rigidity, akinesia; oculogyric crises/status dystonicus; dysautonomia and severe disability in many cases (pqac-00000001, pqac-00000007, pqac-00000018) | CSF: raised HVA with normal 5-HIAA; HVA:5-HIAA ratio typically **5.0–13.0** (normal 1.0–4.0), or practical cutoff **>4**; DaTScan/SPECT: absent or markedly reduced basal nuclei uptake; MRI may be normal or show mild delayed myelination/white-matter abnormalities/prominent frontotemporal spaces; diagnosis confirmed by WES/gene panel/WGS showing pathogenic **SLC6A3** variants (pqac-00000018, pqac-00000019) | Limited response to standard pharmacotherapy; tetrabenazine and benzodiazepines used for chorea/dyskinesia; dopamine agonists such as pramipexole/ropinirole sometimes used; gabapentin may help stiffness; limited or no response to levodopa; DBS and intrathecal baclofen reported with limited benefit; preclinical gene therapy and pharmacochaperone approaches under development (pqac-00000018, pqac-00000024, pqac-00000035) | Ng et al., 2023, https://doi.org/10.3390/cells12131737; Ng et al., 2023, https://doi.org/10.1002/mds.29416 (pqac-00000001, pqac-00000035) |
| Infantile parkinsonism-dystonia due to **DRD1** loss of function | **DRD1** | Autosomal recessive in reported case (homozygous variant) (pqac-00000008, pqac-00000009) | Severe infantile parkinsonism-dystonia with frequent oculogyric crises, dysautonomia, global neurodevelopmental impairment; paucity of spontaneous movement, hypomimia, truncal hypotonia with variable limb tone, prolonged generalized dystonia, feeding impairment, reflux, constipation, sweating, chronic nasal congestion; failed to sit/roll/babble (pqac-00000009, pqac-00000010) | Trio WGS identified homozygous **DRD1** c.110C>A (p.T37K), absent from gnomAD; CSF neurotransmitters/AADC activity were normal, with slight increase in HVA:5-HIAA noted in supplementary data; MRI referenced in supplementary materials; functional assays showed markedly reduced D1 receptor signaling/ligand binding (pqac-00000008, pqac-00000009, pqac-00000010, pqac-00000013) | No clinical response to levodopa up to 10 mg/kg/day; numerous D1 agonists failed to rescue the cellular defect, matching lack of dopaminergic benefit clinically; modest benefit from some tone-modifying agents and transdermal clonidine reported (pqac-00000008, pqac-00000010, pqac-00000012) | Reid et al., 2023, https://doi.org/10.3390/cells12071046 (pqac-00000009, pqac-00000008) |
| Infantile dystonia-parkinsonism type 2 (PKDYS2); parkinsonism-dystonia-2; brain dopamine-serotonin vesicular transport disease | **SLC18A2** | Autosomal recessive (reported homozygous variants) (pqac-00000014, pqac-00000017) | Onset in early infancy; global developmental delay, generalized hypotonia, hyperkinetic movements/dystonia, parkinsonism, oculogyric crises, temperature instability/autonomic features, severe speech and motor impairment, feeding/swallowing problems; many remain nonambulatory and dependent for all activities (pqac-00000014, pqac-00000015, pqac-00000016, pqac-00000017) | WES identified homozygous **SLC18A2** variants including frameshift **c.1107dup p.(Val370Serfs*91)** and splice-site **c.1122+2T>C**; EEG may show no epileptiform activity; brain MRI can be unremarkable/normal; CSF testing was planned but not available in one 2026 report (pqac-00000014, pqac-00000015, pqac-00000017) | Levodopa often ineffective or may worsen symptoms; pramipexole can give partial/initial benefit (head support, swallowing, breathing, reduced dystonic episodes) but adverse effects may limit use; valproate mild or unclear benefit; amantadine no clear benefit; methylphenidate may transiently improve alertness/head support but can worsen dystonia/side effects (pqac-00000014, pqac-00000015, pqac-00000017) | Kaasalainen et al., 2024, https://doi.org/10.1155/2024/4767647 (pqac-00000014, pqac-00000015) |


*Table: This table summarizes Mendelian causes discussed in the retrieved evidence for infantile parkinsonism-dystonia and related infantile dystonia-parkinsonism disorders. It compares genes, inheritance, distinguishing clinical features, diagnostic findings, treatment response patterns, and recent references supported by the available evidence snippets.*