Pure autonomic failure
diseaseOn this page
Also known as Bradbury Eggleston syndromeBradbury-Eggleston syndromeidiopathic orthostatic hypotensionidiopathic orthostatic hypotension (a symptom)orthostatic hypotension (a symptom)PAFPure dysautonomiaPure idiopatic dysautonomia
Summary
Pure autonomic failure (MONDO:0018608) is a disease and 27 clinical trials. Top therapeutic interventions include midodrine, droxidopa, and sodium chloride. A subtype of autonomic nervous system disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).
At a glance
- Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
- Phenotypes (HPO): 10
- Clinical trials: 27
Clinical features
Epidemiology
Prevalence records
1 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Point prevalence | 1-9 / 1 000 000 | Europe | Validated |
Signs & symptoms
Clinical features (HPO)
10 HPO clinical features (Orphanet curated; top 10 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0000970 | Anhidrosis | Very frequent (80-99%) |
| HP:0001278 | Orthostatic hypotension | Very frequent (80-99%) |
| HP:0012099 | Abnormality of circulating catecholamine level | Very frequent (80-99%) |
| HP:0012332 | Abnormal autonomic nervous system physiology | Very frequent (80-99%) |
| HP:0025142 | Constitutional symptom | Very frequent (80-99%) |
| HP:0000020 | Urinary incontinence | Frequent (30-79%) |
| HP:0001279 | Syncope | Frequent (30-79%) |
| HP:0002019 | Constipation | Frequent (30-79%) |
| HP:0100518 | Dysuria | Frequent (30-79%) |
| HP:0000802 | Impotence | Occasional (5-29%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | pure autonomic failure |
| Mondo ID | MONDO:0018608 |
| MeSH | D054970 |
| Orphanet | 441 |
| ICD-11 | 734022291 |
| SNOMED CT | 84438001 |
| UMLS | C0393911 |
| MedGen | 98293 |
| GARD | 0010428 |
| NORD | 1948 |
| Is cancer (heuristic) | no |
Also known as: Bradbury Eggleston syndrome · Bradbury-Eggleston syndrome · idiopathic orthostatic hypotension · idiopathic orthostatic hypotension (a symptom) · orthostatic hypotension (a symptom) · PAF · Pure dysautonomia · Pure idiopatic dysautonomia
Disease family
This is a subtype of autonomic nervous system disorder. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.
Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › autonomic nervous system disorder › pure autonomic failure
Related subtypes (12): idiopathic peripheral autonomic neuropathy, autonomic neuropathy, autonomic nervous system neoplasm, Frey syndrome, harlequin syndrome, chronic hiccup, baroreflex failure, autonomic dysreflexia, dysautonomia, sympathetic nervous system disorder, parasympathetic nervous system disorder, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
No tiered GWAS variants or ClinVar records for this disease.
Genes & proteins
No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).
Function
No pathway enrichment — requires an associated-gene cohort.
Therapeutics
No druggable-target or therapeutic data for this disease’s cohort.
Clinical trials & evidence
Clinical trials
Clinical trials: 27.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 15 |
| PHASE1 | 6 |
| PHASE3 | 2 |
| EARLY_PHASE1 | 2 |
| PHASE2 | 1 |
| PHASE1/PHASE2 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT01927055 | PHASE3 | TERMINATED | A Clinical Study of Patients With Symptomatic NOH to Assess Sustained Effects of Droxidopa Therapy |
| NCT03829657 | PHASE3 | TERMINATED | Phase 3 Clinical Effect Durability of TD-9855 for Treating Symptomatic nOH in Subjects With Primary Autonomic Failure |
| NCT02705755 | PHASE2 | COMPLETED | TD-9855 Phase 2 in Neurogenic Orthostatic Hypotension (nOH) |
| NCT03482297 | PHASE1/PHASE2 | COMPLETED | Automated Abdominal Binder for Orthostatic Hypotension |
| NCT02897063 | PHASE1 | RECRUITING | Effects of Midodrine and Droxidopa on Splanchnic Capacitance in Autonomic Failure |
| NCT04246437 | PHASE1 | RECRUITING | [18F]F-DOPA Imaging in Patients With Autonomic Failure |
| NCT00179023 | PHASE1 | COMPLETED | The Autonomic Nervous System and Obesity |
| NCT01119417 | PHASE1 | WITHDRAWN | The Role of Endothelin in the Supine Hypertension of Autonomic Failure |
| NCT01292694 | PHASE1 | TERMINATED | Contribution of Angiotensin II to Supine Hypertension in Autonomic Failure |
| NCT02429557 | PHASE1 | COMPLETED | Hemodynamic Mechanisms of Abdominal Compression in the Treatment of Orthostatic Hypotension in Autonomic Failure |
| NCT02591173 | EARLY_PHASE1 | TERMINATED | Blood Pressure Lowering Effects of Angiotensin-(1-7) in Primary Autonomic Failure |
| NCT04620382 | EARLY_PHASE1 | COMPLETED | Effect of Midodrine vs Abdominal Compression on Cardiovascular Risk Markers in Autonomic Failure Patients |
| NCT01799915 | Not specified | RECRUITING | Natural History Study of Synucleinopathies |
| NCT03042988 | Not specified | RECRUITING | Overnight Trials With Heat Stress in Autonomic Failure Patients With Supine Hypertension |
| NCT04782830 | Not specified | RECRUITING | Use of Accelerometer for Quantification of Neurogenic Orthostatic Hypotension Symptoms |
| NCT05489575 | Not specified | RECRUITING | CPAP for the Treatment of Supine Hypertension |
| NCT00178919 | Not specified | COMPLETED | Nitric Oxide and the Autonomic Nervous System |
| NCT00742586 | Not specified | COMPLETED | Autonomic Failure Patients for RNA Blood Sampling |
| NCT00775853 | Not specified | COMPLETED | Biomarkers of Risk of Parkinson Disease |
| NCT01044693 | Not specified | COMPLETED | Nebivolol in the Supine Hypertension of Autonomic Failure |
| NCT01316666 | Not specified | COMPLETED | Norepinephrine Transporter Blockade as a Pathological Biomarker in Neurogenic Orthostatic Hypotension |
| NCT01607268 | Not specified | TERMINATED | Magnetic Resonance Spectroscopy in Autonomic Failure |
| NCT02417415 | Not specified | COMPLETED | Local Heat Stress in Autonomic Failure Patients With Supine Hypertension |
| NCT02640339 | Not specified | COMPLETED | Retinal Abnormalities as Biomarker of Disease Progression and Early Diagnosis of Parkinson Disease |
| NCT03681080 | Not specified | COMPLETED | Concentration and Attentional Deficits in POTS and Other Autonomic Neuropathies |
| NCT04700722 | Not specified | COMPLETED | Synuclein-One Study |
| NCT04875949 | Not specified | COMPLETED | Anti-Cholinergic Receptors Antibodies, Autonomic Profile and Dysautonomia Symptoms in PAF, ALS and POTS (DISAUT-AB) |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| MIDODRINE | 4 | 4 |
| DROXIDOPA | 4 | 2 |
| SODIUM CHLORIDE | 4 | 2 |
| TRIMETHAPHAN | 4 | 2 |
| CAPTOPRIL | 4 | 1 |
| METOPROLOL | 4 | 1 |
| NEBIVOLOL | 4 | 1 |
| PSEUDOEPHEDRINE | 4 | 1 |
| AMPRELOXETINE | 3 | 2 |
| TILARGININE | 3 | 1 |
| BQ-123 | 2 | 1 |
| TALFIRASTIDE | 2 | 1 |
| CHEMBL1593851 | 0 | 2 |
| CHEMBL2365658 | 0 | 1 |
| CHEMBL3526436 | 0 | 1 |