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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 |
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| ==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]] |
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| 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]].
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| 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. | |
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| 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.
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| ===Associated Conditions=== | |
| Some associated conditions that occur with Alport syndrome are [[chronic kidney failure]], and [[proteinuria]].
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| ===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.
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| 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.
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| ==Diagnosis==
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| ===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:
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| * 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.
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| * Persistent [[hematuria]] without evidence of another possibly inherited nephropathy such as [[thin GBM disease]], [[polycystic kidney disease]] or [[IgA nephropathy]].
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| * 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.
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| * A [[mutation]] in a COL4An gene (where n = 3, 4 or 5).
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| * [[Immunohistochemistry|Immunohistochemical]] evidence of complete or partial lack of the Alport [[epitope]] in glomerular, or epidermal basement membranes, or both.
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| * Widespread [[GBM|glomerular basement membrane]] ultrastructural abnormalities, in particular thickening, thinning and splitting.
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| * Ocular lesions including anterior lenticonus, posterior subcapsular [[cataract]], posterior polymorphous dystrophy and [[retinal flecks]].
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| * Gradual progression to [[ESRD]] in the index case of at least two family members.
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| * [[Macrothrombocytopenia]] or [[granulocytic inclusions]].
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| * Diffuse [[leiomyomatosis]] of the [[esophagus]] or [[female genitalia]], or both.
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| ===Symptoms=== | |
| Common symptoms of Alport syndrome include:
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| *[[Hematuria]]
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| *[[Peripheral edema]], [[anasarca]]
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| *Decrease or [[loss of vision]]
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| *[[Difficulty hearing]]
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| *[[Flank pain]]
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| *[[Eye pain]]
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| *[[Lacrimation]]
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| *[[Photophobia]]
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| ===Physical Examination===
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| ====Vital signs====
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| *[[Systemic hypertension]] may be present
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| ====Eyes====
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| [[Fundoscopy]] shows: | |
| *[[Cataract]]s may be present
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| *Subcapsular posterior lens opacities may be present
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| *[[Lenticonus]] may be present
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| *Retinal flecks (dot-and-fleck retinopathy) may be present
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| *Posterior polymorphous corneal dystrophy/corneal epithelial erosions may be present
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| ====Ears====
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| *[[Sensorineural deafness]]
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| ====Extremities====
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| *[[Peripheral edema]] may be present
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| *[[Leimyomatosis]] may be present
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| ====Miscellaneous====
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| *[[Anasarca]] may be present
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| ===Laboratory Findings===
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| ====Urinalysis====
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| *Microscopic [[hematuria]]
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| *[[Pyuria]]
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| *Red cell [[casts]]
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| *Cylindrical [[casts]]
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| *[[Proteinuria]]
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| ====Electrolytes and Metabolic disturbances====
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| *Increased [[BUN]]
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| *Increased [[serum creatinine]] levels
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| *[[Hypoalbuminemia]]
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| ====Biopsy Findings====
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| *Irregularly thin and attenuated [[glomerular basement membrane]] of the kidneys
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| *Splitting of [[glomerular basement membrane]] of the kidneys
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| *Scarring of tubules and interstitium of the kidneys
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| ==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]] |
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| ===Surgery and Device Based Therapy===
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| 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.
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| ===Future or Investigational Therapies===
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| [[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> | |
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| ''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]'' |