Achalasia-Addisonianism-Alacrima Syndrome (AAAS)

Categories: Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Achalasia-Addisonianism-Alacrima Syndrome

MalaCards integrated aliases for Achalasia-Addisonianism-Alacrima Syndrome:

Name: Achalasia-Addisonianism-Alacrima Syndrome 57 25 59 74
Allgrove Syndrome 57 12 53 25 59 74 55
Achalasia-Addisonianism-Alacrimia Syndrome 57 12 75 13 40
Alacrima-Achalasia-Adrenal Insufficiency Neurologic Disorder 57 53 25 74
Triple-a Syndrome 57 12 74 15
Triple a Syndrome 75 53 25 59
Glucocorticoid Deficiency with Achalasia 29 6 72
Aaa Syndrome 53 25 59
Glucocorticoid Deficiency and Achalasia 57 74
Alacrima-Achalasia-Addisonianism 57 74
Addisonian-Achalasia Syndrome 57 74
Hypoadrenalism with Achalasia 57 74
Aaas 57 74
Aaa 53 25
Acth-Resistant Adrenal Insufficiency with Achalasia and Alacrima 74
Acth-Resistant Adrenal Insufficiency, Achalasia and Alacrima 57
Adrenal Insufficiency-Achalasia-Alacrima Syndrome 59
Achalasia Addisonianism Alacrimia Syndrome 53
Achalasia Addisonianism Alacrima Syndrome 37
Adrenal Cortical Hypofunction 72
Addisonian Achalasia Syndrome 53
Achalasia-Addisonian Syndrome 25
Achalasia Alacrima Syndrome 53
Achalasia-Alacrima Syndrome 25
Adrenal Gland Hypofunction 72
Quaternary a Syndrome 59
Adrenal Insufficiency 44
Allgrove's Syndrome 74
Double a Syndrome 59
2a Syndrome 59
3a Syndrome 59
4a Syndrome 59


Orphanet epidemiological data:

triple a syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;


autosomal recessive

progressive disorder
onset in early childhood
adrenal insufficiency usually develops later (first decade)
neurologic symptoms may develop decades later
variable neurologic phenotype


achalasia-addisonianism-alacrima syndrome:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive childhood onset


External Ids:

Disease Ontology 12 DOID:0050602
OMIM 57 231550
KEGG 37 H00257
MeSH 44 D000309
MESH via Orphanet 45 C536008 C536009
ICD10 via Orphanet 34 E27.4
UMLS via Orphanet 73 C0271742 C2931084
Orphanet 59 ORPHA869
UMLS 72 C0001623 C0271742 C0405580

Summaries for Achalasia-Addisonianism-Alacrima Syndrome

Genetics Home Reference : 25 Triple A syndrome is an inherited condition characterized by three specific features: achalasia, Addison disease, and alacrima. Achalasia is a disorder that affects the ability to move food through the esophagus, the tube that carries food from the throat to the stomach. It can lead to severe feeding difficulties and low blood sugar (hypoglycemia). Addison disease, also known as primary adrenal insufficiency, is caused by abnormal function of the small hormone-producing glands on top of each kidney (adrenal glands). The main features of Addison disease include fatigue, loss of appetite, weight loss, low blood pressure, and darkening of the skin. The third major feature of triple A syndrome is a reduced or absent ability to secrete tears (alacrima). Most people with triple A syndrome have all three of these features, although some have only two. Many of the features of triple A syndrome are caused by dysfunction of the autonomic nervous system. This part of the nervous system controls involuntary body processes such as digestion, blood pressure, and body temperature. People with triple A syndrome often experience abnormal sweating, difficulty regulating blood pressure, unequal pupil size (anisocoria), and other signs and symptoms of autonomic nervous system dysfunction (dysautonomia). People with this condition may have other neurological abnormalities, such as developmental delay, intellectual disability, speech problems (dysarthria), and a small head size (microcephaly). In addition, affected individuals commonly experience muscle weakness, movement problems, and nerve abnormalities in their extremities (peripheral neuropathy). Some develop optic atrophy, which is the degeneration (atrophy) of the nerves that carry information from the eyes to the brain. Many of the neurological symptoms of triple A syndrome worsen over time. People with triple A syndrome frequently develop a thickening of the outer layer of skin (hyperkeratosis) on the palms of their hands and the soles of their feet. Other skin abnormalities may also be present in people with this condition. Alacrima is usually the first noticeable sign of triple A syndrome, as it becomes apparent early in life that affected children produce little or no tears while crying. They develop Addison disease and achalasia during childhood or adolescence, and most of the neurologic features of triple A syndrome begin during adulthood. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.

MalaCards based summary : Achalasia-Addisonianism-Alacrima Syndrome, also known as allgrove syndrome, is related to adrenal insufficiency, congenital, with 46,xy sex reversal, partial or complete and achalasia, and has symptoms including ataxia and muscle weakness. An important gene associated with Achalasia-Addisonianism-Alacrima Syndrome is AAAS (Aladin WD Repeat Nucleoporin). The drugs Triamcinolone and Propofol have been mentioned in the context of this disorder. Affiliated tissues include testes, pituitary and adrenal gland, and related phenotypes are seizures and achalasia

Disease Ontology : 12 An autosomal recessive disease characterized by achalasia, adrenal insufficiency and alacrima and has material basis in mutations in the AAAS gene that encodes ALADIN within the nuclear envelope and results in dysfunction of the autonomic nervous system.

NIH Rare Diseases : 53 Triple A syndrome is an inherited condition characterized by three specific features: achalasia, Addison disease, and alacrima (a reduced or absent ability to secrete tears). Most people with triple A syndrome have all three of these features, although some have only two. Several authors published descriptions of a more global autonomic disturbance associated with the original three characteristics, leading one author to suggest the name 4A syndrome (adrenal insufficiency, achalasia, alacrima, autonomic abnormalities). Specific autonomic disturbances described in this syndrome include abnormal pupillary reflexes, poor heart rate variability, and orthostatic hypotension. Affected individuals may also have developmental delay, intellectual disability, speech problems, a small head size, muscle weakness, movement problems, peripheral neuropathy, and optic atrophy. Many of the neurological symptoms of triple A syndrome worsen over time. Triple A syndrome is caused by mutations in the AAAS gene and is inherited in an autosomal recessive pattern. Alacrimia is treated with artificial tears while achalasia may need surgery with either pneumatic dilatation or Heller's myotomy. Adrenal insufficiency is treated with glucocorticoid and if necessary mineralocorticoid replacement.

KEGG : 37
Achalasia-Addisonianism-Alacrima (AAA) syndrome, also known as triple-A syndrome, is a rare autosomal recessive disorder characterized by alacrima, achalasia, adrenal insufficiency and autonomic instability caused by mutation in the AAAS gene on 12q13. Recently, it has been reported that mutations in GMPPA cause alacrima, achalasia, and mental retardation syndrome (AAMR), that shows similarity to the triple A syndrome.

UniProtKB/Swiss-Prot : 74 Achalasia-addisonianism-alacrima syndrome: An autosomal recessive disorder characterized by adreno-corticotropic hormone (ACTH)-resistant adrenal failure, achalasia of the esophageal cardia and alacrima. The syndrome is associated with variable and progressive neurological impairment involving the central, peripheral, and autonomic nervous system. Other features such as palmoplantar hyperkeratosis, short stature, facial dysmorphy and osteoporosis may also be present.

Wikipedia : 75 Triple-A syndrome or AAA syndrome, is a rare autosomal recessive congenital disorder. In most cases,... more...

More information from OMIM: 231550

Related Diseases for Achalasia-Addisonianism-Alacrima Syndrome

Diseases related to Achalasia-Addisonianism-Alacrima Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 822)
# Related Disease Score Top Affiliating Genes
1 adrenal insufficiency, congenital, with 46,xy sex reversal, partial or complete 32.2 SGPL1 POMC AAAS
2 achalasia 30.9 TRAPPC11 MC2R GMPPA AAAS
3 familial glucocorticoid deficiency 30.6 POMC MC2R
4 glucocorticoid deficiency 1 30.5 POMC MC2R
5 adrenal cortical adenoma 30.3 POMC MC2R
6 adrenal gland disease 29.9 POMC MC2R
7 adrenal rest tumor 29.8 POMC MC2R
8 hypoadrenocorticism, familial 29.5 POMC MC2R
9 obesity, early-onset, with adrenal insufficiency and red hair 12.8
10 secondary adrenal insufficiency 12.8
11 chronic primary adrenal insufficiency 12.5
12 aortic aneurysm, familial abdominal, 1 12.4
13 inherited isolated adrenal insufficiency due to partial cyp11a1 deficiency 12.3
14 genetic chronic primary adrenal insufficiency 12.3
15 acquired chronic primary adrenal insufficiency 12.3
16 nephrotic syndrome, type 14 12.2
17 immunodeficiency 54 12.1
18 adrenal hypoplasia, congenital 11.9
19 intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies 11.8
20 aortic aneurysm 11.7
21 autoimmune addison disease 11.6
22 lipoid congenital adrenal hyperplasia 11.6
23 inclusion body myopathy with paget disease of bone and frontotemporal dementia 11.6
24 autoimmune polyendocrine syndrome, type ii 11.5
25 acth deficiency, isolated 11.5
26 glycerol kinase deficiency 11.5
27 pituitary apoplexy 11.5
28 autoimmune polyendocrine syndrome, type i, with or without reversible metaphyseal dysplasia 11.5
29 stiff-person syndrome 11.5
30 adrenomyodystrophy 11.5
31 glucocorticoid deficiency 4 with or without mineralocorticoid deficiency 11.5
32 classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency 11.4
33 alacrima, achalasia, and mental retardation syndrome 11.4
34 alopecia, neurologic defects, and endocrinopathy syndrome 11.3
35 mental retardation, x-linked, syndromic 17 11.3
36 esophageal disease 11.3
37 idiopathic achalasia 11.3
38 gmppa-cdg 11.2
39 glucocorticoid deficiency 2 11.2
40 glucocorticoid deficiency 5 11.2
41 diamond-blackfan anemia 11.2
42 childhood-onset cerebral x-linked adrenoleukodystrophy 11.2
43 hypoaldosteronism 11.2
44 breast cancer 10.7
45 aneurysm 10.7
46 toxic shock syndrome 10.6
47 hypopituitarism 10.5
48 antiphospholipid syndrome 10.5
49 autosomal recessive disease 10.4
50 lymphoma 10.4

Graphical network of the top 20 diseases related to Achalasia-Addisonianism-Alacrima Syndrome:

Diseases related to Achalasia-Addisonianism-Alacrima Syndrome

Symptoms & Phenotypes for Achalasia-Addisonianism-Alacrima Syndrome

Human phenotypes related to Achalasia-Addisonianism-Alacrima Syndrome:

59 32 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
2 achalasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002571
3 generalized hyperpigmentation 59 32 hallmark (90%) Very frequent (99-80%) HP:0007440
4 adrenal insufficiency 59 32 hallmark (90%) Very frequent (99-80%) HP:0000846
5 visual impairment 59 32 frequent (33%) Frequent (79-30%) HP:0000505
6 short stature 59 32 frequent (33%) Frequent (79-30%) HP:0004322
7 palmoplantar keratoderma 59 32 frequent (33%) Frequent (79-30%) HP:0000982
8 ataxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001251
9 muscular hypotonia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001252
10 hyperreflexia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001347
11 respiratory insufficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0002093
12 developmental regression 59 32 occasional (7.5%) Occasional (29-5%) HP:0002376
13 microcephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000252
14 sensorineural hearing impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000407
15 optic atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0000648
16 motor axonal neuropathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0007002
17 pes cavus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001761
18 anterior hypopituitarism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000830
19 iris coloboma 59 32 occasional (7.5%) Occasional (29-5%) HP:0000612
20 abnormality of the calf musculature 59 32 occasional (7.5%) Occasional (29-5%) HP:0001430
21 plantar hyperkeratosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0007556
22 abnormality of the hypothenar eminence 59 32 occasional (7.5%) Occasional (29-5%) HP:0010486
23 intellectual disability 32 HP:0001249
24 dysarthria 32 HP:0001260
25 muscle weakness 32 HP:0001324
26 global developmental delay 32 HP:0001263
27 abnormality of visual evoked potentials 32 HP:0000649
28 babinski sign 32 HP:0003487
29 decreased circulating aldosterone level 32 HP:0004319
30 decreased circulating cortisol level 32 HP:0008163
31 hyperpigmentation of the skin 32 HP:0000953
32 alacrima 32 HP:0000522
33 orthostatic hypotension 32 HP:0001278
34 palmoplantar hyperkeratosis 32 HP:0000972
35 abnormal autonomic nervous system physiology 32 HP:0012332
36 anisocoria 32 HP:0009916
37 adrenocorticotropin receptor defect 32 HP:0008259

Symptoms via clinical synopsis from OMIM:

Neurologic Central Nervous System:
muscle weakness
Head And Neck Eyes:
optic atrophy
anisocoria due to autonomic dysfunction

Neurologic Peripheral Nervous System:
motor axonal neuropathy

Skin Nails Hair Skin:
hyperkeratosis of the palms and soles
abnormal sweating due to autonomic dysfunction

Muscle Soft Tissue:
distal muscle weakness and atrophy

Laboratory Abnormalities:
schirmer test shows alacrima

Head And Neck Head:

Growth Height:
short stature

Abdomen Gastrointestinal:

abnormal cardiovascular reflexes due to autonomic dysfunction
postural hypotension

Endocrine Features:
adrenocorticotropic hormone (acth)-resistant adrenal insufficiency
glucocorticoid insufficiency
mineralocorticoid insufficiency (in 15%)

Clinical features from OMIM:


UMLS symptoms related to Achalasia-Addisonianism-Alacrima Syndrome:

ataxia, muscle weakness

Drugs & Therapeutics for Achalasia-Addisonianism-Alacrima Syndrome

Drugs for Achalasia-Addisonianism-Alacrima Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 182)
# Name Status Phase Clinical Trials Cas Number PubChem Id
Triamcinolone Approved, Vet_approved Phase 4 124-94-7 31307
Propofol Approved, Investigational, Vet_approved Phase 4 2078-54-8 4943
Celecoxib Approved, Investigational Phase 4 169590-42-5 2662
Xylometazoline Approved, Investigational Phase 4 526-36-3 5709
Megestrol acetate Approved, Investigational, Vet_approved Phase 4 595-33-5 11683
Eplerenone Approved Phase 4 107724-20-9 150310 443872
tannic acid Approved Phase 4 1401-55-4
Benzocaine Approved, Investigational Phase 4 94-09-7, 1994-09-7 2337
Fentanyl Approved, Illicit, Investigational, Vet_approved Phase 4 437-38-7 3345
Ketamine Approved, Vet_approved Phase 4 6740-88-1 3821
Sodium citrate Approved, Investigational Phase 4 68-04-2
Prednisone Approved, Vet_approved Phase 4 53-03-2 5865
Prednisolone phosphate Approved, Vet_approved Phase 4 302-25-0
Methylprednisolone Approved, Vet_approved Phase 4 83-43-2 6741
Methylprednisolone hemisuccinate Approved Phase 4 2921-57-5
Prednisolone Approved, Vet_approved Phase 4 50-24-8 5755
Citric acid Approved, Nutraceutical, Vet_approved Phase 4 77-92-9 311
Cortisone Experimental Phase 4 53-06-5 222786
Prednisolone hemisuccinate Experimental Phase 4 2920-86-7
20 Adrenocorticotropic Hormone Phase 4
21 triamcinolone acetonide Phase 4
22 Triamcinolone diacetate Phase 4
23 Triamcinolone hexacetonide Phase 4
24 Omega 3 Fatty Acid Phase 4
25 Mineralocorticoids Phase 4
26 Contraceptives, Oral Phase 4
27 Contraceptive Agents Phase 4
28 Central Nervous System Stimulants Phase 4
29 Appetite Stimulants Phase 4
Megestrol Phase 4 3562-63-8 3080587 19090
31 Diuretics, Potassium Sparing Phase 4
32 Mineralocorticoid Receptor Antagonists Phase 4
33 Tin Fluorides Phase 4
34 Fluorodeoxyglucose F18 Phase 4
35 Analgesics Phase 4
36 Anesthetics, Intravenous Phase 4
37 Narcotics Phase 4
38 Adjuvants, Anesthesia Phase 4
39 Analgesics, Opioid Phase 4
40 Central Nervous System Depressants Phase 4
41 Anesthetics, General Phase 4
42 Citrate Phase 4
43 Excitatory Amino Acid Antagonists Phase 4
44 Anesthetics, Dissociative Phase 4
45 Excitatory Amino Acids Phase 4
46 Prednisolone acetate Phase 4
47 Neuroprotective Agents Phase 4
48 Methylprednisolone Acetate Phase 4
49 Protective Agents Phase 4
Midodrine Approved Phase 3 133163-28-7, 42794-76-3 4195

Interventional clinical trials:

(show top 50) (show all 213)
# Name Status NCT ID Phase Drugs
1 Effect of Treatment With Stress-Doses Glucocorticoid on Mortality in Patients With ARDS and Relative Adrenal Insufficiency Unknown status NCT00773058 Phase 4 hydrocortisone;placebo
2 Effect of Modified-release Compared to Conventional Hydrocortisone on Fatigue, Measured by Ecological Momentary Assessments; a Pilot Study. Unknown status NCT02282150 Phase 4 Hydrocortisone;Plenadren
3 The Effect of 6-Methyl-Prednisolone on Organ Dysfunction and Mortality of Patients With Unresolving Multiple Organ Dysfunction Syndrome Unknown status NCT00127985 Phase 4 6-methyl-prednisolone
4 Dexamethasone-suppression-test Predicts Later Development of Adrenal Insufficiency After a 14 Days' Course of Prednisone in Healthy Volunteers Completed NCT00975078 Phase 4 prednisone
5 A Randomized Double Blind Cross-over Study of the Effects of Low Dose and High Dose Hydrocortisone Replacement Therapy on Cognition, Quality of Life, Metabolic Profile and Somatosensation in Patients With Secondary Adrenal Insufficiency Completed NCT01546922 Phase 4 Hydrocortisone
6 A Randomized, Controlled, Multi-Centre Trial on the Effects of Dual-release Hydrocortisone Preparations Versus Conventional Glucocorticoid Replacement Therapy in Patients Affected by Primary and Secondary Adrenal Insufficiency. DREAM Trial. Completed NCT02277587 Phase 4 Plenadren;Conventional glucocorticoid therapy
7 Low-dose Hydrocortisone in the Treatment of the Shock of Burned Patients Completed NCT00149123 Phase 4 hydrocortisone 200 mg/day
8 TALENT Endoluminal Stent Graft System for the Treatment of Abdominal Aortic Aneurysms Completed NCT00803075 Phase 4
9 Post Operative Hemodynamic Function After Anesthetic Induction With Etomidate for Cardiac Surgery With ECC. A Prospective, Monocentric, Randomised Double Blind Study Completed NCT00451776 Phase 4 etomidate;propofol
10 Revival of Autochthonous Adrenocortical Stem Cells in Autoimmune Addison's Disease Completed NCT01371526 Phase 4 depot tetracosactide
11 Efficiency and Safety Study of Short-term Prednisone to Treat Moderate and Severe Subacute Thyroiditis Completed NCT01837433 Phase 4 Prednisone 1 week;Prednisone 6 weeks
12 The Effect of Moderate-Dose Steroid Therapy in Sepsis: A Placebo-Controlled, Randomized Study Completed NCT01275638 Phase 4 Prednisolone
13 The Effect of Reduced Corticosteroid Therapy in Patients With Acute Exacerbation of COPD Completed NCT02857842 Phase 4 Prednisolone
14 Determination of Method-specific Normal Cortisol and Adrenal Hormone Responses to the Short Synacthen Test Completed NCT00851942 Phase 4 Synacthen (Tetracosactrin)
15 Steroid Use in Pediatric Fluid and Vasoactive Infusion Dependent Shock - Pilot Study (STRIPES) Completed NCT02044159 Phase 4 Hydrocortisone
16 Comparison of the Risk of Complications and the Quality of Life During Ramadan Fasting in Patients With Corticotrope Deficiency Treated Either by Hydrocortisone or by Prednisolone Completed NCT03585829 Phase 4 Hydrocortisone;Prednisolone
17 Omega-3 Fatty Acids in Bariatric Gastric Bypass Surgery: Effect on Liver Volume, Immune Response and Erythrocyte Function Completed NCT02206256 Phase 4 Omega-3 fatty acid capsules
18 Evaluation of Efficacy and Hypothalamus-pituitary-adrenal Axis Suppression Due to a Single Intrabursal Injection of Corticosteroids in Patients With Shoulder Calcific Tendinopathy Completed NCT01652495 Phase 4 methylprednisolone acetate;Triamcinolone Acetonide
19 Eplerenone in the Management of Abdominal Aortic Aneurysms: A Proof-Of-Concept Randomised Controlled Trial Recruiting NCT02345590 Phase 4 Eplerenone
20 Glucocorticoid Withdrawal and Glucocorticoid-induced Adrenal Insufficiency: a Randomized Controlled Multicenter Trial Recruiting NCT03153527 Phase 4 Prednisone
21 Congenital Adrenal Hyperplasia: Innovative Once Daily Dual Release Hydrocortisone Treatment Recruiting NCT03760835 Phase 4 Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone);Dual release hydrocortisone (plenadren)
22 Comparison of Two Strategies of Glucocorticoid Withdrawal in Rheumatoid Arthritis Patients in Low Disease Activity or Remission. Recruiting NCT02997605 Phase 4 GlucoCorticoid
23 Noninvasive Assessment of Abdominal Aortic Aneurysm (AAA) Wall Structural Integrity and Inflammation as Predictors of Expansion and/or Rupture Recruiting NCT03231397 Phase 4 Assess AAA rupture risk by PET-CTA scans;18F-fludeoxyglucose (FDG)
24 iKanEat: A Randomized-controlled, Multi-center Trial of Megestrol for Chronic Oral Food Refusal in Children 9 Months to 5 Years 6 Months of Age Recruiting NCT03815019 Phase 4 Megestrol Acetate
25 Optimising Steroid Replacement in Patients With Adrenal Insufficiency Enrolling by invitation NCT03282487 Phase 4 Modified release hydrocortisone
26 A Dose-response Study of Markers of Glucocorticoid Effects (DOSCORT): A Single-blinded, Randomized, 2-dose, Cross-over Study Not yet recruiting NCT03210545 Phase 4 Dexamethasone
27 A Combination Study With Sub-Dissociative Ketamine and Fentanyl to Treat Moderate to Severe Pain in the Emergency Department Not yet recruiting NCT03959852 Phase 4 Fentanyl;Ketamine
28 An Open-label, Prospective, Randomized, Controlled Clinical Trial of the Use of Reduced Duration Versus Standard Duration Steroid Replacement Therapy for Acute Adrenal Insufficiency in Patients With Septic Shock Terminated NCT00842933 Phase 4 Corticosteroid;Corticosteroid
29 Phase IV Study to Evaluate the Neuropsychological Effects of Hydrocortisone Substitution in Patients With Partial Adrenal Insufficiency After Traumatic Brain Injury or Subarachnoidal Haemorrhage Terminated NCT01089075 Phase 4 Hydrocortisone;Placebo
30 Hemodynamic and Inflammatory Effects of Abrupt Versus Tapered Corticosteroid Discontinuation in Septic Shock Terminated NCT01150409 Phase 4 hydrocortisone;Normal Saline
31 A Blinded, Placebo Controlled Trial of Hydrocortisone Versus Hydrocortisone Plus Fludrocortisone for the Treatment of Adrenal Insufficiency in Severe Sepsis Withdrawn NCT00368381 Phase 4 Hydrocortisone
32 Comparison of Intramuscular and Intravenous ACTH Stimulation Test in Normal Volunteers Withdrawn NCT03752190 Phase 4 Cosyntropin
33 The Effect of Dexamethasone on Plasma Cortisol Levels, Pain and PONV in Female Patients Undergoing Thyroid Surgery Withdrawn NCT01045876 Phase 4 Dexamethasone
34 Midodrine for the Treatment of Refractory Hypotension in Patients Otherwise Ready for Discharge From the ICU Unknown status NCT01531959 Phase 3 Midodrine;Placebo
35 Magnetic Resonance Imaging of Aortic Aneurysm Instability Unknown status NCT00794092 Phase 2, Phase 3 Sinerem administration
36 Reposição de Esteróides em Crianças Com Choque Séptico Unknown status NCT01047670 Phase 2, Phase 3 Hydrocortisone
37 Expertise Based Randomized Controlled Trial of Open Versus Endovascular Repair of Abdominal Aortic Aneurysms: A Pilot Study Unknown status NCT00358085 Phase 3
38 Phase III Randomized, Double-Blind, Placebo-Controlled Study of Dehydroepiandrosterone Replacement for Primary Adrenal Insufficiency Completed NCT00004313 Phase 3 dehydroepiandrosterone
39 Dehydroepiandrosterone(DHEA) Substitution in Adolescent and Young Women With Central Adrenal Insufficiency. A Multicenter, Randomised Double Blind Trial Completed NCT00575341 Phase 3 Dehydroepiandrosterone;placebo
40 A, Randomised, Controlled, Two-armed, Two-period Cross-over, Multi-centre Phase II/III Study to Assess the Safety and Pharmacokinetics of Once-daily Oral Modified-release Hydrocortisone in Patients With Adrenal Insufficiency Completed NCT00915343 Phase 2, Phase 3 hydrocortisone (modified release), oral tablet 20 and 5 mg;Hydrocortisone, oral tablet, 10 mg
41 A Phase 3 Open-label Study of Infacort® in Neonates, Infants and Children Less Than 6 Years of Age With Adrenal Insufficiency Completed NCT02720952 Phase 3 Infacort®
42 Open-label, Long-term Follow-up of Safety and Biochemical Disease Control of Infacort® in Neonates, Infants and Children With Congenital Adrenal Hyperplasia and Adrenal Insufficiency Previously Enrolled in the Infacort 003 Study Completed NCT02733367 Phase 3 Infacort®
43 Opothérapie Par Hydrocortisone après Injection Unique d'Etomidate Chez le Patient de réanimation Completed NCT00862381 Phase 3 Hydrocortisone;Placebo
44 Phase 3 Study of Hydrocortisone and Fludrocortisone in Glucocorticoid Insufficiency Related to Traumatic Brain Injury Completed NCT01093261 Phase 3 Placebo;Hydrocortisone Fludrocortisone
45 MEA115575: A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study of Mepolizumab Adjunctive Therapy to Reduce Steroid Use in Subjects With Severe Refractory Asthma Completed NCT01691508 Phase 3 Mepolizumab;Placebo;OCS (prednisone/prednisolone)
46 Phase 3 Study of Corticotherapy (Hydrocortisone Alone Versus Hydrocortisone Plus Fludrocortisone) Versus Corticotherapy Plus Intensive Insulin Therapy for Septic Shock Completed NCT00320099 Phase 3 recombinant human insulin;hydrocortisone;fludrocortisone;Hydrocortisone
47 Corticosteroid Therapy of Septic Shock - Corticus. A Multi-National, Prospective, Double-Blind, Randomized, Placebo-Controlled Study Completed NCT00147004 Phase 3 hydrocortisone sodium succinate;Placebo
48 Early Prevention of Broncho-pulmonary Dysplasia and Neonatal Mortality in Very Preterm Infants Using Low Dose of Hydrocortisone: a Randomized Controlled Trial Completed NCT00623740 Phase 3 hydrocortisone;placebo
49 Early Use of Hydrocortisone in Hypotensive Very Low Birth Weight Infants Completed NCT00358748 Phase 3 Hydrocortisone
50 Dopamine Versus Norepinephrine for the Treatment of Vasopressor Dependent Septic Shock Completed NCT00604019 Phase 3 Dopamine;Norepinephrine

Search NIH Clinical Center for Achalasia-Addisonianism-Alacrima Syndrome

Inferred drug relations via UMLS 72 / NDF-RT 51 :

cortisone acetate
hydrocortisone acetate
Hydrocortisone butyrate
hydrocortisone cypionate
hydrocortisone probutate
Hydrocortisone sodium phosphate
Hydrocortisone sodium succinate
hydrocortisone valerate
prednisolone acetate
Prednisolone sodium phosphate
prednisolone tebutate
Triamcinolone Acetonide
triamcinolone diacetate
triamcinolone hexacetonide

Cochrane evidence based reviews: adrenal insufficiency

Genetic Tests for Achalasia-Addisonianism-Alacrima Syndrome

Genetic tests related to Achalasia-Addisonianism-Alacrima Syndrome:

# Genetic test Affiliating Genes
1 Glucocorticoid Deficiency with Achalasia 29 AAAS

Anatomical Context for Achalasia-Addisonianism-Alacrima Syndrome

MalaCards organs/tissues related to Achalasia-Addisonianism-Alacrima Syndrome:

Testes, Pituitary, Adrenal Gland, Brain, Skin, Kidney, Eye

Publications for Achalasia-Addisonianism-Alacrima Syndrome

Articles related to Achalasia-Addisonianism-Alacrima Syndrome:

(show top 50) (show all 140)
# Title Authors PMID Year
Mutant WD-repeat protein in triple-A syndrome. 9 38 8 71
11062474 2000
Triple A syndrome: genotype-phenotype assessment. 38 8 71
12752575 2003
Axonal neuropathy with unusual pattern of amyotrophy and alacrima associated with a novel AAAS mutation p.Leu430Phe. 8 71
18628786 2008
Progressive bulbospinal amyotrophy in triple A syndrome with AAAS gene mutation. 8 71
11914417 2002
Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. 8 71
11159947 2001
Spectrum of mutations of the AAAS gene in Allgrove syndrome: lack of mutations in six kindreds with isolated resistance to corticotropin. 9 38 71
11701718 2001
Allgrove syndrome: an autosomal recessive syndrome of ACTH insensitivity, achalasia and alacrima. 9 38 8
1850671 1991
Allgrove syndrome in a Mexican American family is caused by an ancestral mutation derived from North Africa. 38 71
18261130 2008
A case of Allgrove (Triple A) syndrome associated with renal ectopia. 38 8
12150219 2002
Linkage disequilibrium in inbred North African families allows fine genetic and physical mapping of triple A syndrome. 38 8
10951524 2000
Segregation of Allgrove (triple-A) syndrome in Puerto Rican kindreds with chromosome 12 (12q13) polymorphic markers. 38 8
9285947 1997
Allgrove syndrome: documenting cholinergic dysfunction by autonomic tests. 38 8
8757578 1996
Molecular insights into inherited ACTH resistance syndromes. 9 8
18407210 1994
Mutations in GMPPA cause a glycosylation disorder characterized by intellectual disability and autonomic dysfunction. 71
24035193 2013
Genotypic heterogeneity and clinical phenotype in triple A syndrome: a review of the NIH experience 2000-2005. 8
16098009 2005
Estimating the age of rare disease mutations: the example of Triple-A syndrome. 71
15173230 2004
Progressive bulbospinal amyotrophy in triple A syndrome with AAAS gene mutation. 8
12473793 2002
Linkage of the gene for the triple A syndrome to chromosome 12q13 near the type II keratin gene cluster. 8
8968764 1996
The "4A" syndrome: adrenocortical insufficiency associated with achalasia, alacrima, autonomic and other neurological abnormalities. 8
7895750 1995
Familial adrenal insufficiency, achalasia, alacrima, peripheral neuropathy, microcephaly, normal plasma very long chain fatty acids, and normal muscle mitochondrial respiratory chain enzymes. 8
8006362 1994
Familial glucocorticoid deficiency with achalasia of the cardia associated with mixed neuropathy, long-tract degeneration and mild dementia. 8
1537368 1992
Three sibs with achalasia and alacrimia: a separate entity different from triple-A syndrome. 8
2817011 1989
Familial achalasia with absent tear production. 8
3351712 1988
Familial achalasia associated with adrenocortical insufficiency, alacrima, and neurological abnormalities. 8
3565479 1987
Infantile achalasia associated with deficient tear production. 8
4067228 1985
Glucocorticoid and partial mineralocorticoid deficiency associated with achalasia. 8
6243664 1980
Familial glucocorticoid deficiency with achalasia of the cardia and deficient tear production. 8
78049 1978
Familial achalasia with pulmonary complications in children. 8
4695913 1973
Hereditary adrenocortical unresponsiveness to adrenocorticotropic hormone. 8
4342294 1972
Tissue-specific expression and subcellular localization of ALADIN, the absence of which causes human triple A syndrome. 9 38
19322026 2009
Heterogeneity in the molecular basis of ACTH resistance syndrome. 9 38
18426811 2008
[Allgrove syndrome in the mainland of China: clinical report and mutation analysis]. 9 38
17880786 2007
Allgrove syndrome with features of familial dysautonomia: a novel mutation in the AAAS gene. 9 38
16938764 2006
Mutations of the AAAS gene in an Indian family with Allgrove's syndrome. 9 38
16937455 2006
Familial occurrence of adrenocortical insufficiency in two brothers with Allgrove syndrome. A case report of 4A (Allgrove) syndrome with epilepsy and a new AAAS gene mutation. 9 38
16264411 2005
Molecular cloning and characterization of AAAS-V2, a novel splice variant of human AAAS. 9 38
16022285 2005
Idiopathic achalasia is not allelic to alacrima achalasia adrenal insufficiency syndrome at the ALADIN locus. 9 38
15843079 2005
The diagnosis of adrenal insufficiency in a patient with Allgrove syndrome and a novel mutation in the ALADIN gene. 9 38
15690314 2005
Two cases of Allgrove syndrome with mutations in the AAAS gene. 9 38
15516781 2004
Triple-A syndrome with prominent ophthalmic features and a novel mutation in the AAAS gene: a case report. 9 38
15217518 2004
[From gene to disease; adrenocortical insufficiency, achalasia and disrupted tear secretion: Allgrove syndrome]. 9 38
12497758 2002
Proteomic analysis of the mammalian nuclear pore complex. 9 38
12196509 2002
A broad range of symptoms in allgrove syndrome: single center experience in Southeast Anatolia. 38
31435881 2019
Endoscopic Management of Recurrent Dysphagia in a Patient With Allgrove Syndrome. 38
27683965 2019
Clinical decision making and application of an active rehabilitation program for a person with the neuromuscular symptoms of Allgrove syndrome: a case report. 38
30501443 2018
Allgrove syndrome: case report of 7 years old boy from Bahawalpur. 38
30108399 2018
Per-oral endoscopic myotomy for esophageal achalasia in a case of Allgrove syndrome. 38
29383495 2018
Clinical and molecular report of c.1331 + 1G > A mutation of the AAAS gene in a Moroccan family with Allgrove syndrome: a case report. 38
29866068 2018
Allgrove syndrome and motor neuron disease. 38
30069287 2018
Mycobacterium Fortuitum infection associated with achalasia. 38
30325493 2018

Variations for Achalasia-Addisonianism-Alacrima Syndrome

ClinVar genetic disease variations for Achalasia-Addisonianism-Alacrima Syndrome:

6 (show top 50) (show all 51)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 AAAS NM_015665.6(AAAS): c.938T> C (p.Val313Ala) single nucleotide variant Pathogenic rs773601814 12:53702802-53702802 12:53309018-53309018
2 AAAS NC_000012.12: g.53306793_53321761del deletion Pathogenic
3 AAAS NM_015665.6(AAAS): c.1331+1G> A single nucleotide variant Pathogenic rs150511103 12:53701835-53701835 12:53308051-53308051
4 AAAS NM_015665.6(AAAS): c.251G> A (p.Trp84Ter) single nucleotide variant Pathogenic rs754637718 12:53714349-53714349 12:53320565-53320565
5 AAAS NM_015665.6(AAAS): c.1288C> T (p.Leu430Phe) single nucleotide variant Pathogenic rs121918551 12:53701879-53701879 12:53308095-53308095
6 AAAS NM_015665.6(AAAS): c.1087+1G> A single nucleotide variant Pathogenic rs1035139364 12:53702508-53702508 12:53308724-53308724
7 AAAS NM_015665.6(AAAS): c.43C> A (p.Gln15Lys) single nucleotide variant Pathogenic rs121918549 12:53715207-53715207 12:53321423-53321423
8 AAAS NM_015665.6(AAAS): c.400-2A> G single nucleotide variant Pathogenic 12:53708926-53708926 12:53315142-53315142
9 AAAS NM_015665.6(AAAS): c.980dup (p.Ser328fs) duplication Pathogenic rs387906326 12:53702760-53702760 12:53308976-53308976
10 AAAS NM_015665.6(AAAS): c.1432C> T (p.Arg478Ter) single nucleotide variant Pathogenic rs121918548 12:53701482-53701482 12:53307698-53307698
11 AAAS NM_015665.6(AAAS): c.934C> T (p.Arg312Ter) single nucleotide variant Pathogenic rs121918547 12:53702942-53702942 12:53309158-53309158
12 AAAS NM_015665.6(AAAS): c.1140_1143TCTG[1] (p.Ser382fs) short repeat Pathogenic/Likely pathogenic rs770214071 12:53702253-53702256 12:53308469-53308472
13 AAAS NM_015665.6(AAAS): c.787T> C (p.Ser263Pro) single nucleotide variant Pathogenic/Likely pathogenic rs121918550 12:53703408-53703408 12:53309624-53309624
14 AAAS NM_015665.6(AAAS): c.936_937del (p.Val313Leufs) deletion Likely pathogenic 12:53702803-53702804 12:53309019-53309020
15 AAAS NM_015665.6(AAAS): c.679T> C (p.Leu227=) single nucleotide variant Conflicting interpretations of pathogenicity rs80027466 12:53708092-53708092 12:53314308-53314308
16 AAAS NM_015665.6(AAAS): c.1450C> G (p.Leu484Val) single nucleotide variant Uncertain significance rs764298213 12:53701464-53701464 12:53307680-53307680
17 AAAS NM_015665.6(AAAS): c.912T> G (p.Ala304=) single nucleotide variant Uncertain significance rs138749872 12:53702964-53702964 12:53309180-53309180
18 AAAS NM_015665.6(AAAS): c.63C> G (p.His21Gln) single nucleotide variant Uncertain significance rs200408293 12:53715187-53715187 12:53321403-53321403
19 AAAS NM_015665.6(AAAS): c.259G> T (p.Val87Leu) single nucleotide variant Uncertain significance rs766985003 12:53709559-53709559 12:53315775-53315775
20 AAAS NM_015665.6(AAAS): c.258T> A (p.Asp86Glu) single nucleotide variant Uncertain significance rs749899811 12:53709560-53709560 12:53315776-53315776
21 AAAS NM_015665.6(AAAS): c.11T> C (p.Leu4Pro) single nucleotide variant Uncertain significance rs886049652 12:53715239-53715239 12:53321455-53321455
22 AAAS NM_015665.6(AAAS): c.1498C> T (p.Arg500Trp) single nucleotide variant Uncertain significance rs886049649 12:53701416-53701416 12:53307632-53307632
23 AAAS NM_015665.6(AAAS): c.1416+8C> T single nucleotide variant Uncertain significance rs370325323 12:53701621-53701621 12:53307837-53307837
24 AAAS NM_015665.6(AAAS): c.1301G> A (p.Arg434Gln) single nucleotide variant Uncertain significance rs112579822 12:53701866-53701866 12:53308082-53308082
25 AAAS NM_015665.6(AAAS): c.996+12C> T single nucleotide variant Uncertain significance rs200312077 12:53702732-53702732 12:53308948-53308948
26 AAAS NM_015665.6(AAAS): c.939C> T (p.Val313=) single nucleotide variant Uncertain significance rs79881935 12:53702801-53702801 12:53309017-53309017
27 AAAS NM_015665.6(AAAS): c.663C> G (p.Thr221=) single nucleotide variant Uncertain significance rs886049650 12:53708108-53708108 12:53314324-53314324
28 AAAS NM_015665.6(AAAS): c.200C> T (p.Thr67Ile) single nucleotide variant Uncertain significance rs1114167372 12:53714400-53714400 12:53320616-53320616
29 AAAS NM_015665.6(AAAS): c.1249+8G> A single nucleotide variant Uncertain significance rs200834285 12:53702058-53702058 12:53308274-53308274
30 AAAS NM_015665.6(AAAS): c.1244T> C (p.Met415Thr) single nucleotide variant Uncertain significance rs200871966 12:53702071-53702071 12:53308287-53308287
31 AAAS NM_015665.6(AAAS): c.843C> G (p.Pro281=) single nucleotide variant Uncertain significance rs145196232 12:53703033-53703033 12:53309249-53309249
32 AAAS NM_015665.6(AAAS): c.1300C> T (p.Arg434Ter) single nucleotide variant Uncertain significance 12:53701867-53701867 12:53308083-53308083
33 AAAS NM_015665.6(AAAS): c.936-2A> G single nucleotide variant Uncertain significance 12:53702806-53702806 12:53309022-53309022
34 TBX19 NM_005149.3(TBX19): c.210G> T (p.Met70Ile) single nucleotide variant Uncertain significance 1:168260404-168260404 1:168291166-168291166
35 TBX19 NM_005149.3(TBX19): c.477G> C (p.Leu159Phe) single nucleotide variant Uncertain significance 1:168262390-168262390 1:168293152-168293152
36 AAAS NM_015665.6(AAAS): c.1591C> T (p.Leu531Phe) single nucleotide variant Uncertain significance rs886049647 12:53701323-53701323 12:53307539-53307539
37 AAAS NM_015665.6(AAAS): c.894C> T (p.Asp298=) single nucleotide variant Uncertain significance rs199636211 12:53702982-53702982 12:53309198-53309198
38 AAAS NM_015665.6(AAAS): c.333C> T (p.Ser111=) single nucleotide variant Uncertain significance rs146770218 12:53709185-53709185 12:53315401-53315401
39 AAAS NM_015665.6(AAAS): c.124-4A> G single nucleotide variant Uncertain significance rs886049651 12:53714480-53714480 12:53320696-53320696
40 AAAS NM_015665.6(AAAS): c.-84G> A single nucleotide variant Uncertain significance rs886049653 12:53715333-53715333 12:53321549-53321549
41 AAAS NM_015665.6(AAAS): c.1566C> T (p.Ser522=) single nucleotide variant Uncertain significance rs886049648 12:53701348-53701348 12:53307564-53307564
42 AAAS NM_015665.6(AAAS): c.-130C> T single nucleotide variant Uncertain significance rs149864679 12:53715379-53715379 12:53321595-53321595
43 AAAS NM_015665.6(AAAS): c.-73G> A single nucleotide variant Uncertain significance rs561616104 12:53715322-53715322 12:53321538-53321538
44 AAAS NM_015665.6(AAAS): c.65A> G (p.Asn22Ser) single nucleotide variant Uncertain significance rs774899476 12:53715185-53715185 12:53321401-53321401
45 AAAS NM_015665.6(AAAS): c.1515T> C (p.Pro505=) single nucleotide variant Likely benign rs35282133 12:53701399-53701399 12:53307615-53307615
46 AAAS NM_015665.6(AAAS): c.234G> A (p.Lys78=) single nucleotide variant Likely benign rs145519240 12:53714366-53714366 12:53320582-53320582
47 AAAS NM_015665.5(AAAS): c.*32C> T single nucleotide variant Likely benign rs138994144 12:53701241-53701241 12:53307457-53307457
48 AAAS NM_015665.6(AAAS): c.414T> C (p.Asp138=) single nucleotide variant Likely benign rs11540353 12:53708910-53708910 12:53315126-53315126
49 AAAS NM_015665.6(AAAS): c.1597G> A (p.Gly533Arg) single nucleotide variant Likely benign rs34451260 12:53701317-53701317 12:53307533-53307533
50 AAAS NM_015665.6(AAAS): c.1557T> C (p.Thr519=) single nucleotide variant Likely benign rs112987708 12:53701357-53701357 12:53307573-53307573

UniProtKB/Swiss-Prot genetic disease variations for Achalasia-Addisonianism-Alacrima Syndrome:

# Symbol AA change Variation ID SNP ID
1 AAAS p.Gln15Lys VAR_012804 rs121918549
2 AAAS p.His160Arg VAR_012805 rs129783112
3 AAAS p.Ser263Pro VAR_012806 rs121918550

Expression for Achalasia-Addisonianism-Alacrima Syndrome

Search GEO for disease gene expression data for Achalasia-Addisonianism-Alacrima Syndrome.

Pathways for Achalasia-Addisonianism-Alacrima Syndrome

GO Terms for Achalasia-Addisonianism-Alacrima Syndrome

Cellular components related to Achalasia-Addisonianism-Alacrima Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear chromatin GO:0000790 9.33 SMARCD2 SMARCC2 APTX
2 SWI/SNF complex GO:0016514 8.96 SMARCD2 SMARCC2
3 nuclear envelope GO:0005635 8.92 PGRMC2 NUP62 IPO11 AAAS

Biological processes related to Achalasia-Addisonianism-Alacrima Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 biosynthetic process GO:0009058 9.32 GMPPB GMPPA
2 nucleocytoplasmic transport GO:0006913 9.26 NUP62 AAAS
3 ATP-dependent chromatin remodeling GO:0043044 9.16 SMARCD2 SMARCC2
4 nucleosome disassembly GO:0006337 8.96 SMARCD2 SMARCC2
5 DNA ligation GO:0006266 8.62 LIG1 APTX

Sources for Achalasia-Addisonianism-Alacrima Syndrome

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
32 HPO
33 ICD10
34 ICD10 via Orphanet
38 LifeMap
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
55 Novoseek
58 OMIM via Orphanet
62 PubMed
71 Tocris
73 UMLS via Orphanet
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