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> | 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> Triple A stands for achalasia-addisonianism-alacrima syndrome. | ||
==Historical Perspective== | ==Historical Perspective== | ||
| Line 25: | Line 25: | ||
==Pathophysiology== | ==Pathophysiology== | ||
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 [[esophagus|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.<ref>{{cite journal |author=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. |title=Genotype heterogeneity and clinical phenotype in triple A syndrome |journal=Clinical Genetics |volume=68 |year=2005 |pages=215–221 |doi=10.1111/j.1399-0004.2005.00482.x |pmid=16098009}}</ref> | |||
===Genetics=== | ===Genetics=== | ||
Achalasia-addisonian 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/> | |||
===Associated Conditions=== | |||
* [[Adrenal cortex insufficiency]] | |||
* [[Nelson syndrome]] | |||
* [[Autonomic neuropathy]] | |||
==Natural History, Complications and Prognosis== | |||
===Natural History=== | |||
Achalasia-addisonian syndrome is a progressive disorder that can take years to develop the full blown clinical picture.<ref name=aaagp/> | |||
==Prognosis== | |||
The syndrome is highly variable. Managed effectively, affected individuals can have a normal lifespan and bear children. | |||
==Diagnosis== | ==Diagnosis== | ||
===Symptoms=== | |||
* [[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> | |||
* [[Difficulty swallowing]] - [[dysphagia]] | |||
* [[Nausea]] | |||
* [[Vomiting]] | |||
* [[Weakness]] | |||
* [[Mental retardation]] | |||
===Physical Examination=== | |||
====Eye==== | |||
* [[Alacrima]], [[dry eyes]] | |||
====Neurologic==== | |||
* Mild [[mental retardation]]<ref name=aaagp/> | |||
===Laboratory Findings=== | |||
* [[Hypoglycemia]] ([[low blood sugar]]) is often mentioned as an early sign.<ref name=aaagp>{{cite journal |author=Prpic, I.; Huebner, A.; Persic, M.; Handschugg, K.; Pavletic, M. |title=Triple A syndrome: genotype-phenotype assessment |journal=Clinical Genetics |volume=63 |year=2003 |pages=414–417}}</ref> | |||
* [[Cortisol]] - decreased | |||
===Imaging=== | |||
====CT==== | |||
{| align="center" | |||
|+ '''Achalasia in a patient with Allgrove syndrome''' | |||
! | |||
|-valign="top" | |||
| [[Image:Allgrove-syndrome-001.jpg|150 px]] | |||
| [[Image:Allgrove-syndrome-002.jpg|150 px]] | |||
|} | |||
====MRI==== | |||
[[Image:Achalasia-addisonian_syndrome.jpg|thumb|center|MRI of the brain of 12 year-old boy with triple-A syndrome showing hypoplastic lacrimal glands (yellow arrows.)]] | |||
==See also== | ==See also== | ||
Latest revision as of 18:22, 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] Triple A stands for achalasia-addisonianism-alacrima syndrome.
Historical Perspective
Achalasia-addisonian syndrome was discovered by Jeremy Allgrove and colleagues in 1978.
Pathophysiology
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.[3]
Genetics
Achalasia-addisonian syndrome is associated with mutations in the AAAS gene, which encodes a protein known as ALADIN (ALacrima Achalasia aDrenal Insuffiency Neurologic disorder).[4][5] In 2000, Huebner et al. mapped the syndrome to a 6 cM interval on human chromosome 12q13 near the type II keratin gene cluster.[6] Since inheritance and gene for the association is known, early diagnosis can allow genetic counseling.[7]
Associated Conditions
Natural History, Complications and Prognosis
Natural History
Achalasia-addisonian syndrome is a progressive disorder that can take years to develop the full blown clinical picture.[8]
Prognosis
The syndrome is highly variable. Managed effectively, affected individuals can have a normal lifespan and bear children.
Diagnosis
Symptoms
- Alacrima is usually the earliest manifestation.[7]
- Difficulty swallowing - dysphagia
- Nausea
- Vomiting
- Weakness
- Mental retardation
Physical Examination
Eye
Neurologic
Laboratory Findings
- Hypoglycemia (low blood sugar) is often mentioned as an early sign.[8]
- Cortisol - decreased
Imaging
CT
|
|
MRI
See also
References
- ↑ 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.
- ↑ 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.
- ↑ 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) - ↑ 7.0 7.1 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.
- ↑ 8.0 8.1 8.2 Prpic, I.; Huebner, A.; Persic, M.; Handschugg, K.; Pavletic, M. (2003). "Triple A syndrome: genotype-phenotype assessment". Clinical Genetics. 63: 414&ndash, 417.