ORPHA:869
Triple A syndrome
Also known as: 2A syndrome · 3A syndrome · 4A syndrome · AAA syndrome · Achalasia-addisonianism-alacrima syndrome · Adrenal insufficiency-achalasia-alacrima syndrome · Allgrove syndrome · Double A syndrome · Quaternary A syndrome
Query health: suspect — Only one of 2 strategies returned hits (phrase).
Publications
24,850
Trials
0
Interventional, condition-specific
Researchers
1,223
Distinct authors in sample
Gene link
AAAS, NDC1
Definitive
Readiness
3/6
Stages with a signal
Clinical definition (Orphanet)
Triple A syndrome is a very rare multisystem disease characterized by adrenal insufficiency with isolated glucocorticoid deficiency, achalasia, alacrima, autonomic dysfunction and neurodegeneration.
How rare: <1 / 1 000 000 — fewer than one in a million. In a city the size of Kolkata, that might mean on the order of fifteen people.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0009279
- MeSH:C536008
- OMIM:231550
- UMLS:C0271742
- NCIT:C131005
Additional Mondo synonyms (4)
achalasia-addisonianism-alacrima syndrome · adrenal insufficiency-achalasia-alacrima syndrome · quaternary A syndrome · triple-a syndrome
Research stages
Trial readiness signals
Where this condition sits on an open-data research pipeline — not how close a treatment is, and not medical advice. Empty stages often mean “not in these databases under this Mondo ID,” not “impossible.”
3/6 stages with a signal
No matched interventional trial; the gene is known and literature exists — preclinical or natural-history work may still be the practical next step.
- Gene identifiedPresent
Definitive — AAAS, NDC1
- LiteraturePresent
24,850 matched papers (17,452 in last 10 years) Source
- Phenotype characterisedPresent
58 HPO annotations (e.g. Palmoplantar keratoderma; Visual impairment; Optic atrophy) Source
- Animal modelNot found
No Alliance genotype “model of” associations via Monarch for these Mondo IDs
- Orphan designationNot found
No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source
- Interventional trialNot found
No matched interventional trial under our ClinicalTrials.gov rules
Biology
Genes and phenotypes
Gene–disease validity from GenCC, plus phenotypes and animal models joined from Monarch Initiative via Mondo ID — not a clinical diagnosis aid.
Do we know what causes it?
Yes — we know a specific gene responsible (AAAS, NDC1).
GenCC classification: Definitive.
Phenotypes (Monarch / HPO)
58
Associated phenotypes · MONDO:0009279
- Palmoplantar keratoderma
- Visual impairment
- Optic atrophy
- Keratoconjunctivitis sicca
- Intellectual disability
Showing 5 of 58 — open Monarch for the full list.
Animal models (Monarch / Alliance)
None returned for this Mondo ID. Empty here is not proof that no model organism work exists under another name or gene.
Monarch fetch 2026-07-27
Therapies
Designations, candidates, and chemicals
FDA OOPD and EMA orphan designations, Open Targets clinical candidates, and CTD chemical associations via MyDisease.info. These never change the interventional-trial headline.
Orphan designation (FDA · EMA)
No designation matched this disease via UMLS or preferred name on the FDA OOPD mirror or EMA orphan register. Absence here is not proof that none exists under another wording.
Open Targets candidates
No drugs or clinical candidates returned for this Mondo ID on Open Targets.
CTD chemicals (MyDisease.info)
No CTD chemical associations returned for this Mondo ID.
Literature
Is anyone studying this?
24,850
24,850 papers — among the better-studied rare conditions, though still a fraction of common-disease literature (breast cancer: over 700,000). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.
24,850 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 59 (publications denominator n=3967).
17,452 in the last 10 years · low confidence
Phrase hits: 2,245 · MeSH hits: 0
Who's working on it?
1,223
Distinct author names in 200 sampled papers — named people below.
Who's working on it?
No interventional trial matched this name; these authors publish on it in the sampled literature — a practical starting point for contact.
- 01Huebner A6 papers · 2025
Department of PaediatricsUniversity Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Papers in Europe PMC - 02Koehler K6 papers · 2025
Department of PaediatricsUniversity Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Papers in Europe PMC - 03Domes G3 papers · 2025
Department of Biological and Clinical Psychology, University of Trier, Trier, Germany.
Papers in Europe PMC - 04
- 05Meyer J3 papers · 2025
Department of Neurobehavioral Genetics, University of Trier, Johanniterufer 15, 54290, Trier, Germany.
Papers in Europe PMC - 06Quitter F3 papers · 2025
Department of Pediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Papers in Europe PMC - 07Wang W3 papers · 2026
Department of Orthopedic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Chaoyang District, Beijing, 100020, China.
Papers in Europe PMC - 08Abdullah MA2 papers · 2025
Department of Paediatric Endocrinology and Diabetes, Gaafar Ibn Auf Paediatric Tertiary Hospital, Khartoum 11114, Sudan.
Papers in Europe PMC - 09Agdere L2 papers · 2019
Department of Pediatric Endocrinology, New York Methodist Hospital, Brooklyn, NY, USA.
Papers in Europe PMC - 10Ali S2 papers · 2026
Department of Biological and Biomedical Sciences, The Aga Khan University, Karachi, Pakistan.
Papers in Europe PMC
Clinical research
Is a treatment being tested?
0
interventional trials for this specific condition
No interventional trial testing a treatment matched this specific condition name on ClinicalTrials.gov (observational studies and pan-disease registries are listed separately when present).
Data as of 9 September 2026 · last trial check 9 September 2026
No matched interventional trials. This is true for 77.2% of diseases in the trials denominator (5501 of 7126). Here are the researchers publishing on it.
low confidence · 38.6th percentile (trials denominator)
Recruiting interventional trials
From the matched ClinicalTrials.gov set
No interventional trial testing a treatment was found for this specific condition name on ClinicalTrials.gov.
See who's working on it — people publishing on this disease are often the practical next contact when no trial is listed.
Other registries (secondary)
Broader net from EU CTIS, ISRCTN, and ICTRP when available — deduped against ClinicalTrials.gov IDs already counted above. Dual-model LLM relevance gates what we keep. These rows are not added to the interventional headline.
raw 101 · after dedupe 101 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 61 · dropped 40 · fetched 2026-07-27
Source notes: ictrp: Error: ICTRP public search unavailable (WHO portal is SPA-only; SOAP needs partnership). Tried: https://apps.who.int/tri
No secondary-registry studies passed dual-model relevance for this condition name (after dedupe).
Uncertain / not reviewed (61)
- isrctn·ISRCTN78380445·Recruiting·A clinical trial testing a new treatment called mRNA-4194 for people with Lynch syndrome
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN15375673·Recruiting·Long Covid and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) study
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN15681288·Recruiting·Restoring intestinal symbiosis for efficacy in IBS
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN49366748·No longer recruiting·A phase II study to test the safety and effects of BC-006 Injection in adults with obesity
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN15479264·Recruiting·A phase II trial of CY-101 in participants with adrenocortical cancer
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN85528745·No longer recruiting·The intrauterine environment during the luteal phase of the menstrual cycle
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN90362708·Recruiting·Bleximenib absorption, metabolism, and excretion in participants with acute leukemia
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN62461807·No longer recruiting·A study of a vaccine against Nipah Virus in adults aged 18 to 55 years in Bangladesh
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN37340032·Recruiting·A study of bleximenib, venetoclax and azacitidine for treatment of participants with newly diagnosed acute myeloid leukemia (cAMeLot-2)
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN11926317·Recruiting·A study of JNJ-78278343 in combination with JNJ-95298177 for treatment of prostate cancer
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN20573724·Recruiting·A study to assess the safety and efficacy of an experimental malaria vaccine by infecting vaccinated and unvaccinated volunteers with malaria parasites
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN67752226·No longer recruiting·A pilot and feasibility study comparing vaginal continence devices and pelvic floor muscle training (PFMT) versus PFMT only for female stress urinary incontinence
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN24865912·No longer recruiting·Evaluate the efficacy, safety and dose-response of S-337395
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN99654100·No longer recruiting·A first-in-human phase I/II study to evaluate the safety, tolerability, anti-cancer activity and metabolism of SN38-SPL9111 (DEP®-SN38), an SN38 dendrimer conjugate, in patients with advanced solid tumours.
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN45104480·Recruiting·A modular, multi-part, multi-arm, open-label, phase I/II study to evaluate the safety and tolerability of GRWD5769 alone and in combination with anticancer treatments in patients with solid malignancies
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN45965456·Suspended·Randomised, open-label international trial with Verapamil alone compared with Verapamil plus another immunotherapy for people with newly diagnosed type 1 diabetes
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN13559330·No longer recruiting·To test the efficacy, safety, and immunogenicity of the influenza virus vaccines (modRNA) in a human influenza B challenge model in healthy adult participants
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN85112396·No longer recruiting·A study in volunteers to look at the safety and tolerability of the new test medicine GUB014295 and how it is taken up by the body when given as a single and multiple dose by injection
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN16927703·No longer recruiting·A study to evaluate nipocalimab and certolizumab combination therapy in participants with active rheumatoid arthritis
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN12036902·No longer recruiting·Understanding how two common respiratory infections interact in the nose of healthy adults: Respiratory Syncytial Virus and Streptococcus pneumoniae
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN12278036·No longer recruiting·A study of bleximenib in combination with acute myeloid leukemia-directed therapies
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN12242529·No longer recruiting·How common is late-onset Pompe disease and limb girdle muscular dystrophy 2a in children and young people and adults treated for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A cross-sectional study.
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN15842444·Recruiting·Assessing the safety of atezolizumab being directly administered to the bladder in bladder cancer patients undergoing radical cystectomy
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN15569205·Stopped·A clinical study to learn whether a new drug, TPN-101, is safe when given to AGS patients
skipped — Beyond per-disease secondary LLM cap
- isrctn·ISRCTN13649456·No longer recruiting·A study of three malaria vaccines to prevent the transmission of malaria in adults in Mali: TBVax2
skipped — Beyond per-disease secondary LLM cap
Where to find support
Condition-specific patient organisations, when Orphanet lists them, are on the disease’s Orphanet page. We also link umbrella groups that support undiagnosed and ultra-rare families.
Orphanet entry for Triple A syndrome — check Associations / patient organisations on that page.
India — NPRD
Last verified 2026-07-26This ORPHAcode is not on our curated NPRD list (direct or Mondo-parent match). That does not decide clinical eligibility; families in India should ask a notified Centre of Excellence about current coverage.
Hand-curated for this project. ORPHAcode mappings are best-effort and may be incomplete or imprecise for umbrella categories. Parent (Mondo) matches mean the policy lists a broader category — confirm eligibility with a Centre of Excellence. Financial entitlements summarised from public policy statements and may change. This is not official government guidance.
How we counted this
Europe PMC query (preferred label + any corrected label + Orphanet and Mondo exact synonyms, stoplisted; unioned with resolved MeSH labels when available). UMLS / OMIM / NCIT cross-references are stored on the overview but are not added to the query string.
("Triple A syndrome" OR "2A syndrome" OR "3A syndrome" OR "4A syndrome" OR "AAA syndrome" OR "Achalasia-addisonianism-alacrima syndrome" OR "Adrenal insufficiency-achalasia-alacrima syndrome" OR "Allgrove syndrome" OR "Double A syndrome" OR "Quaternary A syndrome" OR "triple-a syndrome") OR (MESH:"Achalasia Addisonianism Alacrimia syndrome") OR ("AAAS" OR "AAAS syndrome" OR "AAAS-related" OR "NDC1" OR "NDC1 syndrome" OR "NDC1-related")MeSH descriptor terms unioned into the query: Achalasia Addisonianism Alacrimia syndrome
ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"Triple A syndrome" OR "2A syndrome" OR "3A syndrome" OR "4A syndrome" OR "AAA syndrome" OR "Achalasia-addisonianism-alacrima syndrome" OR "Adrenal insufficiency-achalasia-alacrima syndrome" OR "Allgrove syndrome" OR "Double A syndrome" OR "Quaternary A syndrome" OR "triple-a syndrome" OR "Achalasia Addisonianism Alacrimia syndrome"
Study-type breakdown: 0 interventional · 0 observational · 0 expanded access. Only interventional studies enter the trial headline.
Query health: suspect — strategies attempted: phrase, mesh; with hits: phrase
Run this search on ClinicalTrials.gov
Confidence reasoning
- Preferred label is short or not clearly distinctive
- No synonyms dropped by stoplist
- No label/synonym collisions with other diseases in this corpus
- Publication count (24850) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity
Ingested 2026-07-26T02:29:23.617Z