AAA
MCID: TRP001
MIFTS: 50

Triple-a Syndrome (AAA) malady

Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Endocrine diseases, Fetal diseases, Reproductive diseases categories
Download this MalaCard

Summaries for Triple-a Syndrome

About this section


Fully expand this MalaCard
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 based summary: Triple-a Syndrome, also known as allgrove syndrome, is related to achalasia and abdominal aortic aneurysm, and has symptoms including diffuse/generalised skin hyperpigmentation/melanoderma, megaesophagus/cardiospasm/congenital dilation of the esophagus/achalasia and cortico-adrenal hypoplasia/insufficiency. An important gene associated with Triple-a Syndrome is AAAS (achalasia, adrenocortical insufficiency, alacrimia), and among its related pathways are Glucocorticoid receptor regulatory network and AMPK Enzyme Complex Pathway. Affiliated tissues include skin, kidney and adrenal gland.

NIH Rare Diseases:42 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

Descriptions from OMIM:46 231550,615510

Aliases & Classifications for Triple-a Syndrome

About this section
Sources:
8Disease Ontology, 9diseasecard, 42NIH Rare Diseases, 21Genetics Home Reference, 46OMIM, 10DISEASES, 44Novoseek, 48Orphanet, 62UMLS, 35MESH via Orphanet, 26ICD10 via Orphanet, 63UMLS via Orphanet
See all sources

Triple-a Syndrome, Aliases & Descriptions:

Name: Triple-a Syndrome 8 10
Allgrove Syndrome 8 42 21 44 48
Aaa Syndrome 42 21 48 62
Alacrima-Achalasia-Adrenal Insufficiency Neurologic Disorder 42 21 62
Achalasia-Addisonianism-Alacrimia Syndrome 8 9 46
Triple a Syndrome 42 21 48
Achalasia Addisonianism Alacrimia Syndrome 42 62
Achalasia-Addisonianism-Alacrima Syndrome 21 62
Achalasia-Alacrima Syndrome 21 62
Aaa 42 21
Achalasia - Addisonianism - Alacrima Syndrome 48
Adrenal Insufficiency - Achalasia - Alacrima 48
 
Glucocorticoid Deficiency with Achalasia 62
Addisonian Achalasia Syndrome 42
Achalasia-Addisonian Syndrome 21
Achalasia Alacrimia Syndrome 62
Achalasia-Alacrimia Syndrome 48
Achalasia Alacrima Syndrome 42
Quaternary a Syndrome 48
Double a Syndrome 48
4a Syndrome 48
2a Syndrome 48
3a Syndrome 48


Classifications:



Characteristics (Orphanet epidemiological data):

48
allgrove syndrome:
Inheritance: Autosomal recessive; Prevalence: <1/1000000; Age of onset: Variable


External Ids:

Disease Ontology8 DOID:0050602
MESH via Orphanet35 C536008, C536009
ICD10 via Orphanet26 E27.4
UMLS via Orphanet63 C0271742, C2931084

Related Diseases for Triple-a Syndrome

About this section

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



Diseases related to triple-a syndrome

Symptoms for Triple-a Syndrome

About this section

Symptoms by clinical synopsis from OMIM:

231550

Clinical features from OMIM:

231550,615510

Symptoms:

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

HPO human phenotypes related to Triple-a Syndrome:

(show all 42)
id Description Frequency HPO Source Accession
1 seizures hallmark (90%) HP:0001250
2 generalized hyperpigmentation hallmark (90%) HP:0007440
3 primary adrenal insufficiency hallmark (90%) HP:0008207
4 visual impairment typical (50%) HP:0000505
5 palmoplantar keratoderma typical (50%) HP:0000982
6 short stature typical (50%) HP:0004322
7 microcephaly occasional (7.5%) HP:0000252
8 sensorineural hearing impairment occasional (7.5%) HP:0000407
9 iris coloboma occasional (7.5%) HP:0000612
10 optic atrophy occasional (7.5%) HP:0000648
11 anterior hypopituitarism occasional (7.5%) HP:0000830
12 muscular hypotonia occasional (7.5%) HP:0001252
13 hyperreflexia occasional (7.5%) HP:0001347
14 respiratory insufficiency occasional (7.5%) HP:0002093
15 incoordination occasional (7.5%) HP:0002311
16 developmental regression occasional (7.5%) HP:0002376
17 autosomal recessive inheritance HP:0000007
18 microcephaly HP:0000252
19 alacrima HP:0000522
20 alacrima HP:0000522
21 optic atrophy HP:0000648
22 abnormality of vision evoked potentials HP:0000649
23 hyperpigmentation of the skin HP:0000953
24 palmoplantar hyperkeratosis HP:0000972
25 intellectual disability HP:0001249
26 ataxia HP:0001251
27 dysarthria HP:0001260
28 global developmental delay HP:0001263
29 orthostatic hypotension HP:0001278
30 muscle weakness HP:0001324
31 hyperreflexia HP:0001347
32 dysautonomia HP:0002459
33 achalasia HP:0002571
34 babinski sign HP:0003487
35 progressive disorder HP:0003676
36 hypoaldosteronism HP:0004319
37 short stature HP:0004322
38 motor axonal neuropathy HP:0007002
39 hypocortisolemia HP:0008220
40 adrenocorticotropin (acth) receptor (acthr) defect HP:0008259
41 anisocoria HP:0009916
42 childhood onset HP:0011463

Drugs & Therapeutics for Triple-a Syndrome

About this section

Drug clinical trials:

Search ClinicalTrials for Triple-a Syndrome

Search NIH Clinical Center for Triple-a Syndrome

Genetic Tests for Triple-a Syndrome

About this section

Anatomical Context for Triple-a Syndrome

About this section

MalaCards organs/tissues related to Triple-a Syndrome:

32
Skin, Kidney, Adrenal gland, Eye, Lung, Spinal cord

Animal Models for Triple-a Syndrome or affiliated genes

About this section

Publications for Triple-a Syndrome

About this section

Articles related to Triple-a Syndrome:

(show top 50)    (show all 81)
idTitleAuthorsYear
1
Clinical and genetic characterization of a Chinese patient with triple A syndrome and novel compound heterozygous mutations in the AAAS gene. (23327820)
2013
2
Triple A syndrome in Japan. (23861206)
2013
3
Changes in differential gene expression in fibroblast cells from patients with triple A syndrome under oxidative stress. (23315990)
2013
4
Longitudinal neuropsychological profile in a patient with triple a syndrome. (23691407)
2013
5
A 12 year old boy with recurrent episodes of pneumonia: triple A syndrome. (24834210)
2012
6
Long-term clinical follow-up and molecular genetic findings in eight patients with triple A syndrome. (22538409)
2012
7
Triple A syndrome in a patient with genetic growth hormone insensitivity: phenotypic effects of two genetic disorders. (22269647)
2012
8
X-linked mental retardation with alacrima and achalasia-Triple A syndrome or a new syndrome? (21744492)
2011
9
Two siblings with triple A syndrome and novel mutation presenting as hereditary polyneuropathy. (20931227)
2011
10
Triple-A syndrome. (20687490)
2010
11
Triple A syndrome: 32 years experience of a single centre (1977-2008). (20499090)
2010
12
Triple A syndrome: a novel compound heterozygous mutation in the AAAS gene in an Italian patient without adrenal insufficiency. (20051279)
2010
13
Deficiency of ferritin heavy-chain nuclear import in triple a syndrome implies nuclear oxidative damage as the primary disease mechanism. (19855093)
2009
14
Triple A syndrome: two novel mutations in the AAAS gene. (21686524)
2009
15
Clinical and molecular genetic findings in a 6-year-old Bosnian boy with triple A syndrome. (18551317)
2009
16
Tissue-specific expression and subcellular localization of ALADIN, the absence of which causes human triple A syndrome. (19322026)
2009
17
Triple A syndrome mimicking ALS. (18615337)
2008
18
Late-onset triple A syndrome: a risk of overlooked or delayed diagnosis and management. (18953174)
2008
19
Restoration of nuclear-import failure caused by triple A syndrome and oxidative stress. (18662670)
2008
20
Triple A syndrome with ophthalmic manifestations in two siblings. (17595484)
2007
21
Dysphagia due to triple A syndrome: successful treatment of achalasia by balloon dilatation. (17853339)
2007
22
Unusual presentation of triple A syndrome mimicking SjAPgren's syndrome. (17180297)
2007
23
Sialolithiasis with concurrent sialadenitis in an 18-year-old boy with triple A syndrome. (18076839)
2007
24
Triple-A syndrome--the first Chinese patient with novel mutations in the AAAS gene. (16789645)
2006
25
A novel AAAS gene mutation (p.R194X) in a patient with triple A syndrome. (16543750)
2006
26
Cellular localization of 17 natural mutant variants of ALADIN protein in triple A syndrome - shedding light on an unexpected splice mutation. (16609705)
2006
27
Genotypic heterogeneity and clinical phenotype in triple A syndrome: a review of the NIH experience 2000-2005. (16098009)
2005
28
Triple A syndrome. (16361769)
2005
29
Association of chronic symptomatic neutropenia with the triple A syndrome. (15654281)
2005
30
Triple-A syndrome with prominent ophthalmic features and a novel mutation in the AAAS gene: a case report. (15217518)
2004
31
The triple A syndrome is due to mutations in ALADIN, a novel member of the nuclear pore complex. (15666842)
2004
32
Myoclonus and generalized digestive dysmotility in triple A syndrome with AAAS gene mutation. (15022193)
2004
33
Oral manifestations of triple A syndrome. (12911870)
2003
34
Achalasia of the cardia in Allgrove's (triple A) syndrome: histopathologic study of 10 cases. (12717251)
2003
35
Triple A syndrome: genotype-phenotype assessment. (12752575)
2003
36
Achalasia--alacrima--ACTH insensitivity syndrome (Triple A syndrome). (12793312)
2003
37
Triple A syndrome--diagnostic and management issues. (12793313)
2003
38
Analysis of the AAAS gene in a Japanese patient with triple A syndrome. (12008750)
2002
39
Progressive bulbospinal amyotrophy in triple A syndrome with AAAS gene mutation. (11914417)
2002
40
Clinical and novel molecular findings in a 6.8-year-old Turkish boy with triple A syndrome. (11815731)
2001
41
Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. (11159947)
2001
42
Triple A syndrome mimicking cystic fibrosis. (10714761)
2000
43
Xerostomia in patients with triple A syndrome--a newly recognised finding. (11131343)
2000
44
Linkage disequilibrium in inbred North African families allows fine genetic and physical mapping of triple A syndrome. (10951524)
2000
45
Triple A syndrome--clinical aspects and molecular genetics. (11196451)
2000
46
High-resolution transcript map of the region spanning D12S1629 and D12S312 at chromosome 12q13: triple A syndrome-linked region. (11042153)
2000
47
Adrenal insufficiency after achalasia in the triple-A syndrome. (8775483)
1996
48
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
49
Variant of the Triple A syndrome. (7945119)
1994
50
Achalasia-alacrima-ACTH insensitivity syndrome (Triple-A-syndrome). (8253654)
1993

Variations for Triple-a Syndrome

About this section

UniProtKB/Swiss-Prot genetic disease variations for Triple-a Syndrome:

64
id Symbol AA change Variation ID SNP ID
1AAASp.Gln15LysVAR_012804
2AAASp.His160ArgVAR_012805
3AAASp.Ser263ProVAR_012806rs121918550

Clinvar genetic disease variations for Triple-a Syndrome:

6 (show all 13)
id Gene Name Type Significance SNP ID Assembly Location
1AAASNM_015665.5(AAAS): c.934C> T (p.Arg312Ter)single nucleotide variantPathogenicrs121918547GRCh37Chr 12, 53702942: 53702942
2AAASNM_015665.5(AAAS): c.1432C> T (p.Arg478Ter)single nucleotide variantPathogenicrs121918548GRCh37Chr 12, 53701482: 53701482
3AAASNM_015665.5(AAAS): c.980dupT (p.Ser328Ilefs)duplicationPathogenicrs387906326GRCh37Chr 12, 53702759: 53702760
4AAASAAAS, IVS4AS, A-G, -2single nucleotide variantPathogenic
5AAASAAAS, IVS14DS, G-A, +1single nucleotide variantPathogenic
6AAASNM_015665.5(AAAS): c.43C> A (p.Gln15Lys)single nucleotide variantPathogenicrs121918549GRCh37Chr 12, 53715207: 53715207
7AAASNM_015665.5(AAAS): c.787T> C (p.Ser263Pro)single nucleotide variantPathogenicrs121918550GRCh37Chr 12, 53703408: 53703408
8AAASAAAS, IVS11, G-A, +1single nucleotide variantPathogenic
9GMPPANM_013335.3(GMPPA): c.295C> T (p.Arg99Ter)single nucleotide variantPathogenicrs397518460GRCh37Chr 2, 220366625: 220366625
10GMPPANM_013335.3(GMPPA): c.1000A> C (p.Thr334Pro)single nucleotide variantPathogenicrs397518461GRCh37Chr 2, 220370982: 220370982
11GMPPANM_013335.3(GMPPA): c.545G> A (p.Gly182Asp)single nucleotide variantPathogenicrs397518462GRCh37Chr 2, 220368860: 220368860
12GMPPAGMPPA, 1-BP DEL, 210AdeletionPathogenic
13GMPPAGMPPA, TRP214TERsingle nucleotide variantPathogenic

Expression for genes affiliated with Triple-a Syndrome

About this section
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

About this section

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

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.5SMARCD1, POMC
2
Show member pathways
9.4SMARCD1, SMARCD2
3
Show member pathways
Prostate Cancer37
Integrated Cancer pathway37
Steroid Biosynthesis37
9.4SMARCD1, SMARCD2
4
Show member pathways
Development Ligand dependent activation of the ESR1 AP 1 pathway60
9.4SMARCD1, SMARCD2
5
Show member pathways
9.4SMARCD1, SMARCD2

Compounds for genes affiliated with Triple-a Syndrome

About this section

GO Terms for genes affiliated with Triple-a Syndrome

About this section

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

idNameGO IDScoreTop Affiliating Genes
1SWI/SNF complexGO:0165149.1SMARCD1, SMARCD2
2cytoplasmGO:0057378.1IPO11, AAAS, GMPPA, BRWD1, POMC

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

idNameGO IDScoreTop Affiliating Genes
1chromatin remodelingGO:0063389.4SMARCD1, SMARCD2
2nucleosome disassemblyGO:0063379.3SMARCD1, SMARCD2
3regulation of transcription from RNA polymerase II promoterGO:0063578.7BRWD1, SMARCD1, SMARCD2

Products for genes affiliated with Triple-a Syndrome

About this section
  • Antibodies
  • Proteins
  • Lysates

Sources for Triple-a Syndrome

About this section
3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet