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
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.
Is anyone studying this?
2,245
2,245 papers have been published on this condition. That is a real research literature — still far smaller than common diseases (breast cancer: over 700,000 papers). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=183) is 38.
2,245 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 38 (publications denominator n=183).
1,195 in the last 10 years · low confidence
Is a treatment being tested?
2
trials for this specific condition
2 interventional trials matched this specific condition name; 1 currently recruiting in our sample.
Data as of 26 July 2026
2 interventional trials — more than 59.2% of diseases in the trials denominator have none at all (151 of 255; this disease is at the 74.7th percentile).
low confidence · 74.7th percentile (trials denominator)
Do we know what causes it?
Yes — we know a specific gene responsible (AAAS, NDC1).
GenCC classification: Definitive.
Who's working on it?
1,223
Distinct author names in 200 sampled papers — named people below.
Who's working on it?
People publishing on this condition (sampled Europe PMC records). Affiliation is the most recent found in that sample.
- 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
Recruiting interventional trials
Trials testing a treatment from the matched ClinicalTrials.gov set
2 interventional trials matched after quoted-phrase search and title/condition post-filter.
Observational and natural-history studies
1 observational study matches this condition. These do not test a treatment and are not counted in the interventional-trial headline, but they are genuine research: natural-history work often defines the endpoints needed for a future rare-disease trial, and families may be able to enroll.
None of the matched observational studies is currently listed as recruiting.
Where to find support
We do not yet link condition-specific patient organisations. These umbrella groups support undiagnosed and ultra-rare families:
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 below 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"
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" OR "AAAS" OR "NDC1"
Interventional trials matched via: phrase (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).
Study-type breakdown: 2 interventional · 1 observational · 0 expanded access. Only interventional studies enter the trial headline.
Cross-references (from Mondo): MESH:C536008 OMIM:231550 UMLS:C0271742 NCIT:C131005
Query health: ok — strategies attempted: phrase, mesh, recall-expansion; with hits: phrase, recall-expansion
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 (2245) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity