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{{SK}} Hereditary nephritis; hemorrhagic familial nephritis; X-linked nephropathy and deafness; hematuria-nephropathy-deafness; hereditary deafness and nephropathy
{{SK}} Hereditary nephritis; hemorrhagic familial nephritis; X-linked nephropathy and deafness; hematuria-nephropathy-deafness; hereditary deafness and nephropathy


==Overview==
==[[Alport syndrome overview|Overview]]==
'''Alport syndrome''' is a [[genetic disorder|genetic]] condition characterized by the progressive loss of [[kidney]], eye and ear functioning.  The disorder originates from mutations in critical genes involved in the structure of [[basement membrane]]s.  The presence of [[blood]] in the [[urine]] ([[hematuria]]) is almost always found in this condition.  There is no known cure for this disorder.
==[[Alport syndrome historical perspective|Historical Perspective]]==
 
==[[Alport syndrome pathophysiology |Pathophysiology]]==
==Historical Perspective==
==[[Alport syndrome causes|Causes]]==
Alport syndrome was first identified in a British family by Dr. [[Cecil A. Alport]] in 1927.
==[[Alport syndrome differential diagnosis|Differentiating Alport syndrome from other Diseases]]==
 
==[[Alport syndrome epidemiology and demographics|Epidemiology and Demographics]]==
==Pathophysiology==
==[[Alport syndrome natural history, complications and prognosis|Natural History, Complications and Prognosis]]==
===Genetics===
==Diagnosis==
Alport syndrome is caused by [[mutation]]s in the ''[[COL4A3]]'', ''[[COL4A4]]'', and ''[[COL4A5]]'' [[collagen]] biosynthesis genes.  Mutations in any of these genes prevent the proper production or assembly of the [[type IV collagen]] network, which is an important structural component of the [[glomerular basement membrane]]s in the [[kidney]], inner [[ear]], and [[eye]].
[[Alport syndrome diagnostic criteria|Diagnostic Criteria]] | [[Alport syndrome history and symptoms|History and Symptoms]] | [[Alport syndrome physical examination|Physical Examination]] | [[Alport syndrome laboratory findings|Laboratory Findings]] | [[Alport syndrome echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Alport syndrome other diagnostic studies|Other Diagnostic Studies]]
 
This syndrome can have different inheritance patterns depending on the type of genetic mutation.  In most people with the disorder, the condition is inherited in an [[X-linked]] pattern due to mutations in the ''[[COL4A5]]'' gene.  A condition is considered X-linked if the gene involved in the disorder is located on the [[X chromosome]].
 
Alport syndrome can also be inherited in an [[autosomal recessive]] pattern if both copies of the ''COL4A3'' or ''COL4A4'' gene, located on [[chromosome 2 (human)|chromosome 2]], have been mutated.  Most often, the parents of a child with an autosomal recessive disorder are not affected but are only carriers of one copy of the altered genes.
 
In males, who have only one X chromosome, one altered copy of the ''COL4A5'' gene is sufficient to cause severe Alport syndrome.  This single X chromosome explains why most affected males eventually develop [[chronic kidney failure]].  In females, who have two X chromosomes, a mutation in one copy of the ''COL4A5'' gene usually results in blood in the urine, but most affected females do not develop kidney failure.
 
===Associated Conditions===
Some associated conditions that occur with Alport syndrome are [[chronic kidney failure]], and [[proteinuria]].
 
===Microscopic Pathology===
Basement membranes are thin, sheet-like structures that separate and support cells in many tissues.  When mutations prevent the formation of type IV collagen fibers, the basement membranes of the [[kidneys]] are not able to filter waste products from the blood and create urine properly, which allows blood and [[protein]] to enter into the urine.
 
The abnormalities of type IV collagen in the [[glomerular basement membrane]] cause gradual scarring of the [[kidneys]], eventually leading to [[chronic renal failure]] in many people with the disease.
 
==Diagnosis==  
===Diagnostic criteria===
Gregory et al, 1996, give the following 10 criteria for the diagnosis of Alport syndrome <ref name="pmid8801040">{{cite journal |author=Gregory MC, Terreros DA, Barker DF, Fain PN, Denison JC, Atkin CL |title=Alport syndrome--clinical phenotypes, incidence, and pathology |journal=Contrib Nephrol |volume=117 |issue= |pages=1–28 |year=1996 |pmid=8801040 |doi= |url=}}</ref>. 4 of the 10 criteria must be met for an accurate diagnosis:
* Family history of [[nephritis]] and of unexplained [[hematuria]] in a first degree relative of the [[index case]] or in a male relative linked through any numbers of females.
* Persistent [[hematuria]] without evidence of another possibly inherited nephropathy such as [[thin GBM disease]], [[polycystic kidney disease]] or [[IgA nephropathy]].
* Bilateral [[sensorineural hearing loss]] in the 2000 to 8000 Hz range. The hearing loss develops gradually, is not present in early infancy and commonly presents before the age of 30.
* A [[mutation]] in a COL4An gene (where n = 3, 4 or 5).
* [[Immunohistochemistry|Immunohistochemical]] evidence of complete or partial lack of the Alport [[epitope]] in glomerular, or epidermal basement membranes, or both.
* Widespread [[GBM|glomerular basement membrane]] ultrastructural abnormalities, in particular thickening, thinning and splitting.
* Ocular lesions including anterior lenticonus, posterior subcapsular [[cataract]], posterior polymorphous dystrophy and [[retinal flecks]].
* Gradual progression to [[ESRD]] in the index case of at least two family members.
* [[Macrothrombocytopenia]] or [[granulocytic inclusions]].
* Diffuse [[leiomyomatosis]] of the [[esophagus]] or [[female genitalia]], or both.
 
===Symptoms===
Common symptoms of Alport syndrome include:
*[[Hematuria]]
*[[Peripheral edema]], [[anasarca]]
*Decrease or [[loss of vision]]
*[[Difficulty hearing]]
*[[Flank pain]]
*[[Eye pain]]
*[[Lacrimation]]
*[[Photophobia]]
 
===Physical Examination===
====Vital signs====
*[[Systemic hypertension]] may be present
 
====Eyes====
[[Fundoscopy]] shows:
*[[Cataract]]s may be present
*Subcapsular posterior lens opacities may be present
*[[Lenticonus]] may be present
*Retinal flecks (dot-and-fleck retinopathy) may be present
*Posterior polymorphous corneal dystrophy/corneal epithelial erosions may be present
 
====Ears====
*[[Sensorineural deafness]]
 
====Extremities====
*[[Peripheral edema]] may be present
*[[Leimyomatosis]] may be present
 
====Miscellaneous====
*[[Anasarca]] may be present
 
===Laboratory Findings===
====Urinalysis====
*Microscopic [[hematuria]]
*[[Pyuria]]
*Red cell [[casts]]
*Cylindrical [[casts]]
*[[Proteinuria]]
 
====Electrolytes and Metabolic disturbances====
*Increased [[BUN]]
*Increased [[serum creatinine]] levels
*[[Hypoalbuminemia]]
 
====Biopsy Findings====
*Irregularly thin and attenuated [[glomerular basement membrane]] of the kidneys
*Splitting of [[glomerular basement membrane]] of the kidneys
*Scarring of tubules and interstitium of the kidneys


==Treatment==
==Treatment==
As there is no known cure for the condition, treatments are regimented for the symptoms of the condition.
[[Alport syndrome medical therapy|Medical Therapy]] | [[Alport syndrome surgery|Surgery]] | [[Alport syndrome primary prevention|Primary Prevention]] | [[Alport syndrome secondary prevention|Secondary Prevention]] | [[Alport syndrome cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Alport syndrome future or investigational therapies|Future or Investigational Therapies]]
===Pharmacotherapy===
==Case Studies==
Patients are advised on how to manage the complications of [[chronic kidney failure]] and the [[proteinuria]] that develops.  Often, these symptoms are treated with [[ACE inhibitors]], although they are not always used simply for the [[hypertension]].
:[[Alport syndrome case study one|Case #1]]
 
===Surgery and Device Based Therapy===
Once kidney failure has developed, patients undergo [[dialysis]] or may benefit from a [[kidney transplant]], although this may result in rejection as the new kidney contains normal [[type IV collagen]], which may be recognized as foreign by the immune system.
 
===Future or Investigational Therapies===
[[Gene therapy]] as a possible treatment option has been discussed. <ref name="pmid9150464">{{cite journal |author=Tryggvason K, Heikkilä P, Pettersson E, Tibell A, Thorner P |title=Can Alport syndrome be treated by gene therapy? |journal=Kidney Int. |volume=51 |issue=5 |pages=1493–9 |year=1997 |month=May |pmid=9150464 |doi= |url=}}</ref>


''This article incorporates public domain text from [http://ghr.nlm.nih.gov The U.S. National Library of Medicine]''
''This article incorporates public domain text from [http://ghr.nlm.nih.gov The U.S. National Library of Medicine]''

Revision as of 01:09, 30 September 2012

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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]

Synonyms and keywords: Hereditary nephritis; hemorrhagic familial nephritis; X-linked nephropathy and deafness; hematuria-nephropathy-deafness; hereditary deafness and nephropathy

Overview

Historical Perspective

Pathophysiology

Causes

Differentiating Alport syndrome from other Diseases

Epidemiology and Demographics

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria | History and Symptoms | Physical Examination | Laboratory Findings | Echocardiography or Ultrasound | Other Diagnostic Studies

Treatment

Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

Case Studies

Case #1

This article incorporates public domain text from The U.S. National Library of Medicine

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