AAA
MCID: TRP001
MIFTS: 50

Triple-a Syndrome (AAA) malady

Neuronal, Eye, Endocrine, Fetal categories

Summaries for Triple-a Syndrome

Sources:
21Genetics Home Reference, 43NIH Rare Diseases, 47OMIM, 33MalaCards
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Genetics Home Reference:21 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.

MalaCards: Triple-a Syndrome, also known as allgrove syndrome, is related to achalasia and familial glucocorticoid deficiency, and has symptoms including autosomal recessive inheritance, hypereflexia and seizures/epilepsy/absences/spasms/status epilepticus. An important gene associated with Triple-a Syndrome is AAAS (achalasia, adrenocortical insufficiency, alacrimia), and among its related pathways are Regulation of Glucokinase by Glucokinase Regulatory Protein and Glucocorticoid receptor regulatory network. The compounds [d-trp8]-gamma-msh and alpha-msh have been mentioned in the context of this disorder. Affiliated tissues include skin, spinal cord and kidney.

NIH Rare Diseases:43 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. affected individuals may also have dysautonomia, 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. last updated: 8/16/2010

Description from OMIM:47 231550

Aliases & Classifications for Triple-a Syndrome

Sources:
8Disease Ontology, 10DISEASES, 21Genetics Home Reference, 45Novoseek, 49Orphanet, 9diseasecard, 47OMIM, 43NIH Rare Diseases, 61UMLS, 26ICD10 via Orphanet
See all sources

Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Fetal
Anatomical: Neuronal, Eye, Endocrine


Characteristics (Orphanet epidemiological data):

49
allgrove syndrome:
Inheritance: Autosomal recessive; Prevalence: <1/1000000; Age of onset: Variable


Aliases & Descriptions:

triple-a syndrome 8 10
allgrove syndrome 8 21 45 49
achalasia-addisonianism-alacrimia syndrome 8 9 47
triple a syndrome 43 21 49
aaa syndrome 43 21 49
achalasia-alacrima syndrome 21 61
aaa 43 21
alacrima-achalasia-adrenal insufficiency neurologic disorder 21
achalasia - addisonianism - alacrima syndrome 49
adrenal insufficiency - achalasia - alacrima 49
achalasia addisonianism alacrimia syndrome 43
achalasia-addisonianism-alacrima syndrome 21
glucocorticoid deficiency with achalasia 61
addisonian achalasia syndrome 43
achalasia-addisonian syndrome 21
achalasia alacrima syndrome 43
quaternary a syndrome 49
double a syndrome 49
3a syndrome 49
4a syndrome 49
2a syndrome 49


External Ids:

Disease Ontology8 DOID:0050602
OMIM47 231550
ICD10 via Orphanet26 E27.4

Related Diseases for Triple-a Syndrome

Sources:
17GeneCards, 18GeneDecks
See all sources

Diseases in the triple x syndrome family:

triple-a syndrome

Diseases related to Triple-a Syndrome via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 61)
idRelated DiseaseScoreTop Affiliating Genes
1achalasia30.7MC2R, AAAS, POMC
2familial glucocorticoid deficiency30.6MC2R, POMC
3n syndrome10.6
4abdominal aortic aneurysm10.5
5aortic aneurysm10.5
6multiple endocrine neoplasia10.5
7adrenocortical insufficiency10.4
8achalasia-addisonianism-alacrima syndrome10.4
9axonal neuropathy10.3
10hereditary spastic paraplegia10.3
11idiopathic achalasia10.2
12horseshoe kidney10.2
13adult syndrome10.1
14syringomyelia10.1
15hypoglycemia10.1
16periventricular heterotopia10.1
17autonomic dysfunction10.1
18dysautonomia10.1
19accommodative spasm10.1
20ruptured abdominal aortic aneurysm10.1
21adenocarcinoma10.1
22thyroid medullary carcinoma10.1
23cystic fibrosis10.0
24sialolithiasis10.0
25sialadenitis10.0
26infertility10.0
27triple x syndrome10.0
28char syndrome10.0
29isolated acth deficiency10.0
30acth deficiency10.0
31mental retardation10.0
32dysphagia10.0
33myoclonus10.0
34alacrima, achalasia, and mental retardation syndrome10.0
35alopecia10.0KRT86
36deficiency anemia10.0FTH1
37leukemia10.0XRCC1
38epidermolytic hyperkeratosis10.0KRT81, KRT86
39pachyonychia congenita10.0KRT81, KRT86
40monilethrix10.0KRT81, KRT86
41cholera9.9
42beta thalassemia9.9
43werner syndrome9.9
44bjornstad syndrome9.9
45aplastic anemia9.9
46spinal cord ischemia9.9
47thalassemia9.9
48tuberculosis9.9
49cerebellar degeneration9.9
50dysfibrinogenemia9.9

Graphical network of the top 20 diseases related to Triple-a Syndrome:



Diseases related to triple-a syndrome

Clinical Features for Triple-a Syndrome

Sources:
47OMIM, 49Orphanet
See all sources

Clinical features from OMIM:

231550

Clinical synopsis from OMIM:

231550

Symptoms:

49 (show all 18)
  • autosomal recessive inheritance
  • hypereflexia
  • seizures/epilepsy/absences/spasms/status epilepticus
  • ataxia/incoordination/trouble of the equilibrium
  • respiratory distress/dyspnea/respiratory failure/lung volume reduction
  • hypotonia
  • psychic/psychomotor regression/dementia/intellectual decline
  • mild visual loss/impaired visual acuity
  • optic nerve anomaly/optic atrophy/anomaly of the papilla
  • sensorineural deafness/hearing loss
  • short stature/dwarfism/nanism
  • microcephaly
  • palmoplantar hyperkeratosis/keratoderma
  • hypothalamic-hypophyseal axis functional anomalies/hypopituitarism
  • cortico-adrenal hypoplasia/insufficiency
  • coloboma of iris
  • diffuse/generalised skin hyperpigmentation/melanoderma
  • megaesophagus/cardiospasm/congenital dilation of the esophagus/achalasia

Drugs & Therapeutics for Triple-a Syndrome

Sources:
5CenterWatch, 42NIH Clinical Center, 6ClinicalTrials, 61UMLS, 41NDF-RT
See all sources

Approved drugs:

Search CenterWatch for Triple-a Syndrome

Drug clinical trials:

Search ClinicalTrials for Triple-a Syndrome

Search NIH Clinical Center for Triple-a Syndrome

Search CenterWatch for Triple-a Syndrome

Genetic Tests for Triple-a Syndrome

Anatomical Context for Triple-a Syndrome

Sources:
33MalaCards
See all sources

MalaCards organs/tissues related to Triple-a Syndrome:

33
Skin, Spinal cord, Kidney, Colon, Thyroid, Adrenal gland, Fetal thyroid, Pituitary

Animal Models for Triple-a Syndrome or affiliated genes

Sources:
28inGenious Targeting Laboratory
See all sources

Publications for Triple-a Syndrome

Sources:
51PubMed
See all sources

Articles related to Triple-a Syndrome:

(show top 50)    (show all 89)
idTitleAuthorsYear
1
Prevention of thromboembolism in the patient with acute coronary syndrome and atrial fibrillation: the clinical dilemma of triple therapy. (24284976)
2014
2
Clinical and genetic characterization of a Chinese patient with triple A syndrome and novel compound heterozygous mutations in the AAAS gene. (23327820)
2013
3
The genetic basis of triple A (Allgrove) syndrome in a Greek family. (23073554)
2013
4
The role of lupus anticoagulant and triple marker positivity as risk factors for rethrombosis in patients with primary antiphospholipid syndrome. (23305633)
2013
5
The analysis of second-trimester triple screening for Down syndrome in Chinese normal singleton pregnancies. (23057770)
2012
6
Fetal axillary cystic hygroma: a novel association with triple X syndrome. (23109196)
2012
7
Autism in association with Triple X syndrome. (22311144)
2012
8
Recurrent Johanson-Blizzard syndrome in a triplet pregnancy complicated by urethral obstruction sequence: a clinical, molecular, and immunohistochemical approach. (21711208)
2012
9
X-linked mental retardation with alacrima and achalasia-Triple A syndrome or a new syndrome? (21744492)
2011
10
Qualitative assessment of FMR1 (CGG)n triplet repeat status in normal, intermediate, premutation, full mutation, and mosaic carriers in both sexes: implications for fragile X syndrome carrier and newborn screening. (20168238)
2010
11
Triple A syndrome: a novel compound heterozygous mutation in the AAAS gene in an Italian patient without adrenal insufficiency. (20051279)
2010
12
Two Italian patients with novel AAAS gene mutation expand allelic and phenotypic spectrum of triple A (Allgrove) syndrome. (20447142)
2010
13
Triple A syndrome: two novel mutations in the AAAS gene. (21686524)
2009
14
Tissue-specific expression and subcellular localization of ALADIN, the absence of which causes human triple A syndrome. (19322026)
2009
15
Triple A or Allgrove syndrome. A case report with ophthalmic abnormalities and a novel mutation in the AAAS gene. (19172511)
2009
16
Three siblings with triple A syndrome with a novel frameshift mutation in the AAAS gene and a review of 17 independent patients with the frequent p.Ser263Pro mutation. (18172684)
2008
17
An Alu-mediated rearrangement causing a 3.2kb deletion and a novel two base pair deletion in AAAS gene as the cause of triple A syndrome. (17911039)
2007
18
Molecular mechanism of alpha 1(I)-osteogenesis imperfecta/Ehlers-Danlos syndrome: unfolding of an N-anchor domain at the N-terminal end of the type I collagen triple helix. (16407265)
2006
19
Triple-A syndrome--the first Chinese patient with novel mutations in the AAAS gene. (16789645)
2006
20
Heterogeneity of the triple A syndrome and assessment of a case. (16970037)
2006
21
ALADINI482S causes selective failure of nuclear protein import and hypersensitivity to oxidative stress in triple A syndrome. (16467144)
2006
22
Association of chronic symptomatic neutropenia with the triple A syndrome. (15654281)
2005
23
The triple &quot;a&quot; syndrome confirmed by molecular analysis: a case report of 7-year-old boy. (15625433)
2005
24
Failure of selective termination and dexamethasone rescue therapy to arrest HELLP syndrome in a midtrimester triplet gestation with one triploid fetus. (16147843)
2005
25
Triple-a syndrome: a rare etiology of adult achalasia. (15810622)
2005
26
Acute colonic pseudo-obstruction (Ogilvie's Syndrome) following caesarean section for triplets. (16147743)
2005
27
Triple-x syndrome accompanied by congenital adrenal hyperplasia: case report. (15641277)
2004
28
Myoclonus and generalized digestive dysmotility in triple A syndrome with AAAS gene mutation. (15022193)
2004
29
Three children with triple A syndrome due to a mutation (R478X) in the AAAS gene. (14646395)
2004
30
Achalasia of the cardia in Allgrove's (triple A) syndrome: histopathologic study of 10 cases. (12717251)
2003
31
The nuclear pore complex protein ALADIN is mislocalized in triple A syndrome. (12730363)
2003
32
Analysis of the AAAS gene in a Japanese patient with triple A syndrome. (12008750)
2002
33
A case of Allgrove (Triple A) syndrome associated with renal ectopia. (12150219)
2002
34
Progressive bulbospinal amyotrophy in triple A syndrome with AAAS gene mutation. (12473793)
2002
35
An endocrinopathy characterized by dysfunction of the pituitary-adrenal axis and alopecia universalis: supporting the entity of a triple H syndrome. (12213673)
2002
36
Achalasia, alacrima, adrenal insufficiency, and autonomic dysfunction: double A, triple A, or quaternary A syndrome? (11698772)
2001
37
Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. (11159947)
2001
38
Linkage disequilibrium in inbred North African families allows fine genetic and physical mapping of triple A syndrome. (10951524)
2000
39
Variation in the vitreous phenotype of Stickler syndrome can be caused by different amino acid substitutions in the X position of the type II collagen Gly-X-Y triple helix. (11007540)
2000
40
Achalasia-Alacrima-Acth insentivity syndrome (Triple A syndrome) in a Saudi Family. (17322679)
2000
41
A novel mutation in the CAG triplet region of exon 1 of androgen receptor gene causes complete androgen insensitivity syndrome in a large kindred. (10323385)
1999
42
Triplet pregnancy complicated by a gradual decline in antithrombin-III activity and HELLP syndrome: a case report. (9798357)
1998
43
Segregation of Allgrove (triple-A) syndrome in Puerto Rican kindreds with chromosome 12 (12q13) polymorphic markers. (9285947)
1997
44
Abnormal extracellular matrix in Ehlers-Danlos syndrome type IV due to the substitution of glycine 934 by glutamic acid in the triple helical domain of type III collagen. (9147870)
1996
45
Adrenal insufficiency after achalasia in the triple-A syndrome. (8775483)
1996
46
A novel mutation of the adrenocorticotropin receptor (ACTH-R) gene in a family with the syndrome of isolated glucocorticoid deficiency, but no ACTH-R abnormalities in two families with the triple A syndrome. (7608277)
1995
47
Triple-X syndrome accompanied by single maxillary central incisor: case report. (8378162)
1993
48
An osteopenic nonfracture syndrome with features of mild osteogenesis imperfecta associated with the substitution of a cysteine for glycine at triple helix position 43 in the pro alpha 1(I) chain of type I collagen. (1737847)
1992
49
Three sibs with achalasia and alacrimia: a separate entity different from triple-A syndrome. (2817011)
1989
50
Fetal abnormality (Goldenhar syndrome) occurring in one of triplet infants derived from in vitro fertilization with possible monozygotic twinning. (3160797)
1985

Genetic Variations for Triple-a Syndrome

Sources:
63UniProtKB/Swiss-Prot
See all sources

Genetic disease variations for Triple-a Syndrome:

63
id Symbol AA change Variation SNP ID
1AAASp.Gln15LysVAR_012804
2AAASp.His160ArgVAR_012805
3AAASp.Ser263ProVAR_012806rs121918550

Expression for genes affiliated with Triple-a Syndrome

Sources:
1BioGPS, 15Gene Expression Omnibus DataSets
See all sources
Expression patterns in normal tissues for genes affiliated with Triple-a Syndrome

Search GEO for disease gene expression data for Triple-a Syndrome.

Pathways for genes affiliated with Triple-a Syndrome

Sources:
54Reactome, 38NCBI BioSystems Database, 52QIAGEN, 12EMD Millipore
See all sources

Compounds for genes affiliated with Triple-a Syndrome

Sources:
60Tocris Bioscience, 45Novoseek, 11DrugBank
See all sources

Compounds related to Triple-a Syndrome according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1[d-trp8]-gamma-msh6010.1MC2R, POMC
2alpha-msh6010.1POMC, MC2R
3polynucleotide4510.0LIG1, APTX, XRCC1
4hs 0146010.0POMC, MC2R
5pg 1066010.0POMC, MC2R
6metyrapone60 45 1112.0POMC, MC2R
7shu 911945 6010.9MC2R, POMC
8aminoglutethimide45 1110.7POMC, MC2R

GO Terms for genes affiliated with Triple-a Syndrome

Sources:
16Gene Ontology
See all sources

Cellular components related to Triple-a Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1nuclear envelopeGO:0056359.7AAAS, NUP62, POM121
2npBAF complexGO:0715649.4SMARCC2, SMARCD3, SMARCD1
3nBAF complexGO:0715659.3SMARCD1, SMARCD3, SMARCC2
4SWI/SNF complexGO:0165149.1SMARCD2, SMARCC2, SMARCD3, SMARCD1
5nuclear poreGO:0056439.1AAAS, NUP62, IPO7, POM121

Biological processes related to Triple-a Syndrome according to GeneCards/GeneDecks:

(show all 10)
idNameGO IDScoreTop Affiliating Genes
1nucleocytoplasmic transportGO:00691310.1AAAS, NUP62
2single strand break repairGO:00001210.1APTX, XRCC1
3regulation of glucose transportGO:0108279.9AAAS, NUP62, POM121
4mitotic nuclear envelope disassemblyGO:0070779.9AAAS, NUP62, POM121
5hexose transportGO:0086459.9POM121, NUP62, AAAS
6glucose transportGO:0157589.8AAAS, NUP62, POM121
7nucleosome disassemblyGO:0063379.3SMARCD2, SMARCC2, SMARCD3, SMARCD1
8chromatin remodelingGO:0063389.3SMARCD1, SMARCD3, SMARCC2, SMARCD2
9mitotic cell cycleGO:0002789.2AAAS, NUP62, POM121, LIG1
10regulation of transcription from RNA polymerase II promoterGO:0063579.0SMARCD1, SMARCD3, SMARCC2, SMARCD2

Molecular functions related to Triple-a Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1Ran GTPase bindingGO:0085369.7IPO11, IPO7
2transcription coactivator activityGO:0037138.8SMARCD2, SMARCC2, SMARCD3, SMARCD1

Products for genes affiliated with Triple-a Syndrome

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Sources for Triple-a Syndrome

3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
29IUPHAR
30KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
61UMLS
62UMLS via Orphanet