Achalasia-addisonian syndrome: Difference between revisions
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==Overview== | ==Overview== | ||
Achalasia-addisonian syndrome<ref name=omim>{{OMIM|231550}}</ref> is a rare [[autosome|autosomal]] [[dominance (genetics)|recessive]] [[congenital disorder]]. In most cases, there is no family history of it.<ref>{{cite journal |author=Dusek, Tina; Korsic, Marta; Koehler, Katrin; Perkovic, Zdravko; Huebner, Angela; Korsic, Mirko |title=A Novel AAAS Gene Mutation (p.R194X) in a Patient with Triple A Syndrome |journal=Hormone Research |volume=65 |year=2006 |pages=171–176 |doi=10.1159/000092003 |pmid=16543750}}</ref> The syndrome was discovered by [[Jeremy Allgrove]] and colleagues in 1978. Triple A stands for achalasia-addisonianism-alacrima syndrome. Alacrima is usually the earliest manifestation.<ref name=tas>{{cite journal |author=Bharadia, Lalit; Kalla, Mukesh; Sharma, S K; Charan, Rohit; Gupta, J B; Khan, Firoz |title=Triple A Syndrome |journal=Indian Journal of Gastroenterology |volume=24 |year=2005 |pages=218–9 |pmid=16361770 |issue=5}}</ref> It is a progressive disorder that can take years to develop the full blown clinical picture.<ref name=aaagp/> | Achalasia-addisonian syndrome<ref name=omim>{{OMIM|231550}}</ref> is a rare [[autosome|autosomal]] [[dominance (genetics)|recessive]] [[congenital disorder]]. In most cases, there is no family history of it.<ref>{{cite journal |author=Dusek, Tina; Korsic, Marta; Koehler, Katrin; Perkovic, Zdravko; Huebner, Angela; Korsic, Mirko |title=A Novel AAAS Gene Mutation (p.R194X) in a Patient with Triple A Syndrome |journal=Hormone Research |volume=65 |year=2006 |pages=171–176 |doi=10.1159/000092003 |pmid=16543750}}</ref> The syndrome was discovered by [[Jeremy Allgrove]] and colleagues in 1978. Triple A stands for achalasia-addisonianism-alacrima syndrome. Alacrima is usually the earliest manifestation.<ref name=tas>{{cite journal |author=Bharadia, Lalit; Kalla, Mukesh; Sharma, S K; Charan, Rohit; Gupta, J B; Khan, Firoz |title=Triple A Syndrome |journal=Indian Journal of Gastroenterology |volume=24 |year=2005 |pages=218–9 |pmid=16361770 |issue=5}}</ref> It is a progressive disorder that can take years to develop the full blown clinical picture.<ref name=aaagp/> | ||
==Pathophysiology== | |||
===Genetics=== | |||
Triple-A syndrome is associated with mutations in the [[AAAS (gene)|AAAS]] gene, which encodes a protein known as ALADIN (ALacrima Achalasia aDrenal Insuffiency Neurologic disorder).<ref>{{cite journal |author=Huebner, Angela; Kaindl, A.M.; Knobeloch, K.P.; Petzold, H.; Mann, P.; Koehler, K. |title=The Triple A Syndrome Is Due to Mutations in Aladin, a Novel Member of the Nuclear Pore Complex |journal=Endocrine Research |volume=30 |year=2004 |pages=891–899 |doi=10.1081/ERC-200044138 |pmid=15666842}}</ref><ref name="pmid18953174">{{cite journal |author=Salmaggi A, Zirilli L, Pantaleoni C, ''et al.'' |title=Late-onset triple A syndrome: a risk of overlooked or delayed diagnosis and management |journal=Horm. Res. |volume=70 |issue=6 |pages=364–372 |year=2008 |pmid=18953174 |doi=10.1159/000161867 |url=http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000161867}}</ref> In 2000, Huebner ''et al.'' mapped the syndrome to a 6 cM interval on human chromosome 12q13 near the type II keratin gene cluster.<ref>{{cite journal |author=Huebner A, Yoon SJ, Ozkinay F, ''et al.'' |title=Triple A syndrome--clinical aspects and molecular genetics |journal=Endocr. Res. |volume=26 |issue=4 |pages=751–759 |year=2000 |month=Nov |pmid=11196451 |doi= 10.3109/07435800009048596}}</ref> Since inheritance and gene for the association is known, early diagnosis can allow genetic counseling.<ref name=tas/> | |||
==Characteristics== | ==Characteristics== | ||
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The syndrome is highly variable. Managed effectively, affected individuals can have a normal lifespan and bear children. | The syndrome is highly variable. Managed effectively, affected individuals can have a normal lifespan and bear children. | ||
==See also== | ==See also== | ||
Revision as of 17:27, 13 August 2012
| Triple A syndrome | |
| Classification and external resources | |
| OMIM | 231550 |
|---|---|
| DiseasesDB | 32088 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]
Synonyms and keywords: Triple-A syndrome; Achalasia-Addisonianism-Alacrimia syndrome; Allgrove Syndrome
Overview
Achalasia-addisonian syndrome[1] is a rare autosomal recessive congenital disorder. In most cases, there is no family history of it.[2] The syndrome was discovered by Jeremy Allgrove and colleagues in 1978. Triple A stands for achalasia-addisonianism-alacrima syndrome. Alacrima is usually the earliest manifestation.[3] It is a progressive disorder that can take years to develop the full blown clinical picture.[4]
Pathophysiology
Genetics
Triple-A syndrome is associated with mutations in the AAAS gene, which encodes a protein known as ALADIN (ALacrima Achalasia aDrenal Insuffiency Neurologic disorder).[5][6] In 2000, Huebner et al. mapped the syndrome to a 6 cM interval on human chromosome 12q13 near the type II keratin gene cluster.[7] Since inheritance and gene for the association is known, early diagnosis can allow genetic counseling.[3]
Characteristics
Individuals affected by AAA have adrenal insufficiency due to ACTH resistance, alacrima (absence of tear secretion), and achalasia (a failure of a ring of muscle fibers, such as a sphincter, to relax) of the lower esophageal sphincter at the cardia which delays food going to the stomach and causes dilation of the thoracic esophagus. There may also signs of autonomic dysfunction with AAA, such as pupillary abnormalities, an abnormal reaction to intradermal histamine, abnormal sweating, orthostatic hypotension, and disturbances of the heart rate.[8] Hypoglycemia (low blood sugar) is often mentioned as an early sign.[4] The disorder has also been associated with mild mental retardation.[4]
The syndrome is highly variable. Managed effectively, affected individuals can have a normal lifespan and bear children.
See also
External links
- ↑ Online Mendelian Inheritance in Man (OMIM) 231550
- ↑ Dusek, Tina; Korsic, Marta; Koehler, Katrin; Perkovic, Zdravko; Huebner, Angela; Korsic, Mirko (2006). "A Novel AAAS Gene Mutation (p.R194X) in a Patient with Triple A Syndrome". Hormone Research. 65: 171&ndash, 176. doi:10.1159/000092003. PMID 16543750.
- ↑ 3.0 3.1 Bharadia, Lalit; Kalla, Mukesh; Sharma, S K; Charan, Rohit; Gupta, J B; Khan, Firoz (2005). "Triple A Syndrome". Indian Journal of Gastroenterology. 24 (5): 218–9. PMID 16361770.
- ↑ 4.0 4.1 4.2 Prpic, I.; Huebner, A.; Persic, M.; Handschugg, K.; Pavletic, M. (2003). "Triple A syndrome: genotype-phenotype assessment". Clinical Genetics. 63: 414&ndash, 417.
- ↑ Huebner, Angela; Kaindl, A.M.; Knobeloch, K.P.; Petzold, H.; Mann, P.; Koehler, K. (2004). "The Triple A Syndrome Is Due to Mutations in Aladin, a Novel Member of the Nuclear Pore Complex". Endocrine Research. 30: 891&ndash, 899. doi:10.1081/ERC-200044138. PMID 15666842.
- ↑ Salmaggi A, Zirilli L, Pantaleoni C; et al. (2008). "Late-onset triple A syndrome: a risk of overlooked or delayed diagnosis and management". Horm. Res. 70 (6): 364&ndash, 372. doi:10.1159/000161867. PMID 18953174.
- ↑ Huebner A, Yoon SJ, Ozkinay F; et al. (2000). "Triple A syndrome--clinical aspects and molecular genetics". Endocr. Res. 26 (4): 751&ndash, 759. doi:10.3109/07435800009048596. PMID 11196451. Unknown parameter
|month=ignored (help) - ↑ Brooks, B.P.; Kleta, R.; Stuart, C.; Tuchman, M.; Jeong, A.; Stergiopoulos, S.G.; Bei, T.; Bjornson, B.; Russell, L.; Chanoine, J-P.; Tsagarakis, S.; Kalsner, LR.; Stratakis, CA. (2005). "Genotype heterogeneity and clinical phenotype in triple A syndrome". Clinical Genetics. 68: 215&ndash, 221. doi:10.1111/j.1399-0004.2005.00482.x. PMID 16098009.