Alport syndrome diagnostic criteria: Difference between revisions
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The equivocal or non-characteristic finding of any of the above prompts further work-up until the diagnosis is made or rejected.<ref name="pmid23349312">{{cite journal| author=Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F| title=Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. | journal=J Am Soc Nephrol | year= 2013 | volume= 24 | issue= 3 | pages= 364-75 | pmid=23349312 | doi=10.1681/ASN.2012020148 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23349312 }} </ref> | The equivocal or non-characteristic finding of any of the above prompts further work-up until the diagnosis is made or rejected.<ref name="pmid23349312">{{cite journal| author=Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F| title=Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. | journal=J Am Soc Nephrol | year= 2013 | volume= 24 | issue= 3 | pages= 364-75 | pmid=23349312 | doi=10.1681/ASN.2012020148 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23349312 }} </ref> | ||
In 1996, Gregory and colleagues 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: | In 1996, Gregory and colleagues 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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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Diagnostic criteria
The suspicion of Alport’s syndrome should be present when patients present with persistent hematuria of glomerular origin – with dysmorphic RBC and variable hemoglobin content on analysis.[1] However, family history should always be investigated because knowledge of positive family history alone, along with symptoms of Alport’s syndrome, may be diagnostic with up to 80% sensitivity.[1] The definitive diagnosis of Alport’s syndrome can be made by electron microscopy of a kidney biopsy with immunofluorescent assessment.[2]Under microscopy, characteristic lamellated thinned glomerular basement membrane must be identified for proper diagnosis.[1] For diagnostic purposes, at least one COL4A5 mutation or two COL4A3/COL4A4 must be present for X-linked disease or autosomal recessive disease, respectively.
Genetic testing is recommended by expert opinion in 6 conditions[3]:
- Confirm diagnosis of Alport’s syndrome
- Identify mode of inheritance
- Rule out TBMN in patients with persistent hematuria
- Prognostic outcome according to previously described patterns
- Provide prenatal diagnosis for at-risk pregnant females
- To provide embryo pre-implantation genetic diagnosis
Although genetic testing is up to 90% sensitive for diagnosis of X-linked Alport’s syndrome with heterogeneous COL4A5 mutation, renal impairment with homogeneously mutated COL4A3/COL4A4 should not still not rule out TBMN except after consensus of a multidisciplinary team regarding the clinical manifestations and the histopathological features of the disease per case due to the likelihood of TBMN and concurrent renal impairment due to other etiologies of glomerulonephritis.[1]
The defect of the collagen alpha chains may then be visible using immunofluorescence by H51 monoclonal antibody to NC1 region of the collagen alpha-5 chain to reveal most cases of Alport’s syndrome in affected males and in carrier females.[4][5] If renal biopsy is not possible, the H51 antibody may be used on skin tissue biopsies as well.[4] Auditory lesions are diagnosed using audiometry whose audioscans generate frequencies from 250 Hz to 8000 Hz at a rate of 30s/octave. Audioscans may also identify female carriers of Alport’s syndrome.
In 2013, expert opinion by Savige and colleagues demonstrated a practical approach for the diagnoasis of Alport’s syndrome.[1]
Mandatory Criterion | Persistent Hematuria |
Optional Criteria | Presence of at Least 1 of 4:
|
The equivocal or non-characteristic finding of any of the above prompts further work-up until the diagnosis is made or rejected.[1]
In 1996, Gregory and colleagues give the following 10 criteria for the diagnosis of Alport syndrome. [6] 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).
- Immunohistochemical evidence of complete or partial lack of the Alport epitope in glomerular, or epidermal basement membranes, or both.
- Widespread 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.
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F (2013). "Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy". J Am Soc Nephrol. 24 (3): 364–75. doi:10.1681/ASN.2012020148. PMID 23349312.
- ↑ Streeten BW, Robinson MR, Wallace R, Jones DB (1987). "Lens capsule abnormalities in Alport's syndrome". Arch Ophthalmol. 105 (12): 1693–7. PMID 3689194.
- ↑ McCarthy PA, Maino DM (2000). "Alport syndrome: a review". Clin Eye Vis Care. 12 (3–4): 139–150. PMID 11137428.
- ↑ 4.0 4.1 Yoshioka K, Hino S, Takemura T, Maki S, Wieslander J, Takekoshi Y; et al. (1994). "Type IV collagen alpha 5 chain. Normal distribution and abnormalities in X-linked Alport syndrome revealed by monoclonal antibody". Am J Pathol. 144 (5): 986–96. PMC 1887361. PMID 8178947.
- ↑ Kashtan CE, Michael AF (1993). "Alport syndrome: from bedside to genome to bedside". Am J Kidney Dis. 22 (5): 627–40. PMID 8238007.
- ↑ Gregory MC, Terreros DA, Barker DF, Fain PN, Denison JC, Atkin CL (1996). "Alport syndrome--clinical phenotypes, incidence, and pathology". Contrib Nephrol. 117: 1–28. PMID 8801040.