Alstrom syndrome pathophysiology: Difference between revisions

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The Jackson Laboratory in Bar Harbor, Maine, USA with the University of Southampton, UK isolated the single [[gene]] ([[ALMS1]]) responsible for Alstrőm Syndrome. The gene is [[recessive]] (it must be passed from both parents for the syndrome to manifest).
The Jackson Laboratory in Bar Harbor, Maine, USA with the University of Southampton, UK isolated the single [[gene]] ([[ALMS1]]) responsible for Alstrőm Syndrome. The gene is [[recessive]] (it must be passed from both parents for the syndrome to manifest).


The key features are childhood [[obesity]], [[blindness]] due to congenital cone-rod retinal dystrophy, and [[sensorineural hearing loss]]. Associated [[endocrinology|endocrinologic]] features include [[hyperinsulinemia]], early-onset [[type 2 diabetes]], and [[hypertriglyceridemia]].  Thus, AS shares several features with the common metabolic syndrome, namely [[obesity]], [[hyperinsulinemia]], and [[hypertriglyceridemia]]. Mutations in the [[ALMS1]] gene have been found to be causative for AS with a total of 79 disease-causing mutations having been described.<ref name="pmid18154657">{{cite journal | author=Joy T, Cao H, Black G, Malik R, Charlton-Menys V, Hegele RA, Durrington PN |title=Alstrom syndrome (OMIM 203800): a case report and literature review. | journal=Orphanet Journal of Rare Diseases | year=2007 | volume=2 | issue=1 | pmid = 18154657 | url=http://www.ojrd.com/content/pdf/1750-1172-2-49.pdf | pmc=2266715 |doi=10.1186/1750-1172-2-49 |pages=49}}</ref>
The key features are childhood [[obesity]], [[blindness]] due to congenital cone-rod retinal dystrophy, and [[sensorineural hearing loss]]. Associated [[endocrinology|endocrinologic]] features include [[hyperinsulinemia]], early-onset [[type 2 diabetes]], and [[hypertriglyceridemia]].  Thus, AS shares several features with the common [[metabolic syndrome]], namely [[obesity]], [[hyperinsulinemia]], and [[hypertriglyceridemia]]. Mutations in the [[ALMS1]] gene have been found to be causative for AS with a total of 79 disease-causing mutations having been described.<ref name="pmid18154657">{{cite journal | author=Joy T, Cao H, Black G, Malik R, Charlton-Menys V, Hegele RA, Durrington PN |title=Alstrom syndrome (OMIM 203800): a case report and literature review. | journal=Orphanet Journal of Rare Diseases | year=2007 | volume=2 | issue=1 | pmid = 18154657 | url=http://www.ojrd.com/content/pdf/1750-1172-2-49.pdf | pmc=2266715 |doi=10.1186/1750-1172-2-49 |pages=49}}</ref>


* The cone-rod retinal dystrophy usually develops within the first few weeks after birth and the symptoms include [[nystagmus]] and extreme photodysphoria (light sensitivity). It is progressive and by the second decade of life leads to loss of perception of light (blindness).   
* The cone-rod retinal dystrophy usually develops within the first few weeks after birth and the symptoms include [[nystagmus]] and extreme photodysphoria (light sensitivity). It is progressive and by the second decade of life leads to loss of perception of light (blindness).   
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* About 50% of individuals have delay in early [[developmental milestones]]; intelligence is normal.  
* About 50% of individuals have delay in early [[developmental milestones]]; intelligence is normal.  
* Liver involvement includes elevation of [[transaminase]]s, [[steatosis]], [[hepatosplenomegaly]], and [[steatohepatitis]]. [[Portal hypertension]] and [[cirrhosis]] can lead to [[hepatic encephalopathy]] and life-threatening [[esophageal varices]].  
* Liver involvement includes elevation of [[transaminase]]s, [[steatosis]], [[hepatosplenomegaly]], and [[steatohepatitis]]. [[Portal hypertension]] and [[cirrhosis]] can lead to [[hepatic encephalopathy]] and life-threatening [[esophageal varices]].  
* Pulmonary dysfunction and severe renal disease may also develop.  Pulmonary dysfunction can range from frequent bronchial infections to pulmonary fibrosis and pulmonary hypertension.  Renal disease is progressive and the severity of glomerulosclerosis is highly variable.  [[End-stage renal disease]] ([[ESRD]]) can occur as early as the late teens.
* Pulmonary dysfunction and severe renal disease may also develop.  Pulmonary dysfunction can range from frequent bronchial infections to pulmonary fibrosis and [[pulmonary hypertension]].  Renal disease is progressive and the severity of [[glomerulosclerosis]] is highly variable.  [[End-stage renal disease]] ([[ESRD]]) can occur as early as the late teens.


===Genetics===
===Genetics===
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==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
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[[Category:Genetic Disease]]
[[Category:Genetic Disease]]
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[[Category:Disease]]
[[Category:Disease]]
[[Category:Needs overview]]
[[Category:Needs overview]]
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Latest revision as of 20:04, 14 March 2016

Alstrom syndrome Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]; Raviteja Guddeti, M.B.B.S. [3]

Pathophysiology

The Jackson Laboratory in Bar Harbor, Maine, USA with the University of Southampton, UK isolated the single gene (ALMS1) responsible for Alstrőm Syndrome. The gene is recessive (it must be passed from both parents for the syndrome to manifest).

The key features are childhood obesity, blindness due to congenital cone-rod retinal dystrophy, and sensorineural hearing loss. Associated endocrinologic features include hyperinsulinemia, early-onset type 2 diabetes, and hypertriglyceridemia. Thus, AS shares several features with the common metabolic syndrome, namely obesity, hyperinsulinemia, and hypertriglyceridemia. Mutations in the ALMS1 gene have been found to be causative for AS with a total of 79 disease-causing mutations having been described.[1]

Genetics

ALMS1 encodes a protein whose function is unknown. Mutations in this gene can lead to production of a dysfunctional protein that might be responsible for the signs and symptoms of Alstrom disease. Alström syndrome (AS) is a rare autosomal recessive disease characterized by multi-organ dysfunction.

References

  1. Joy T, Cao H, Black G, Malik R, Charlton-Menys V, Hegele RA, Durrington PN (2007). "Alstrom syndrome (OMIM 203800): a case report and literature review" (PDF). Orphanet Journal of Rare Diseases. 2 (1): 49. doi:10.1186/1750-1172-2-49. PMC 2266715. PMID 18154657.


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