Characterization of the peripheral retinopathy in X-linked and autosomal recessive Alport syndrome

Launceston General Hospital, Patersonia, Tasmania, Australia
Nephrology Dialysis Transplantation (Impact Factor: 3.49). 02/2007; 22(1):104-8. DOI: 10.1093/ndt/gfl607
Source: PubMed

ABSTRACT Alport syndrome is an inherited disease resulting in kidney failure, hearing loss and ocular abnormalities. Alport syndrome is however often unrecognized, and the aim of this study was to characterize the associated but rarely described peripheral retinopathy and determine whether its demonstration was diagnostically helpful.
Index cases were diagnosed with Alport syndrome on renal biopsy in themselves or a family member. Inheritance and affected status were determined using microsatellite markers at the COL4A5 and COL4A3/COL4A4 loci, respectively. Participants' eyes were dilated, and examined with direct and indirect ophthalmoscopy, and slit lamp biomicroscopy by an expert ophthalmologist who was unaware of the patients' disease status.
Ten males and nine females with X-linked Alport syndrome and seven with autosomal recessive disease were studied. Of the 26 patients, 16 had central retinopathy (62%), and 19 patients had peripheral retinopathy (74%). The peripheral changes occurred in both males and females with X-linked and autosomal recessive Alport syndrome, and were more common when renal failure, hearing loss, lenticonus and the central changes were present, but were also noted in 3 X-linked carriers with normal renal function.
The peripheral retinopathy occurs in X-linked and autosomal recessive Alport syndrome even when the central retinopathy is absent. Careful retinal examination and photography that includes the periphery is a safe and inexpensive method that may help in the diagnosis of Alport syndrome especially in carriers of X-linked disease.

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    Pediatric Nephrology 12/2013; 29(3). DOI:10.1007/s00467-013-2682-6 · 2.88 Impact Factor
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    ABSTRACT: Autosomal recessive Alport syndrome (ARAS) is a rare hereditary disease caused by homozygous or compound heterozygous mutations in either the COL4A3 or COL4A4 genes. Failure to diagnose ARAS cases is common, even if detailed clinical and pathological examinations are carried out. As the mutation detection rate for ARAS is unsatisfactory, we sought to develop more reliable diagnostic methods and provide a better description of the clinicopathological characteristics of this disorder. A retrospective analysis of 30 genetically diagnosed patients with ARAS in 24 pedigrees was conducted. The mutation detection strategy comprised three steps: (1) genomic DNA analysis using polymerase chain reaction (PCR) and direct sequencing; (2) mRNA analysis using reverse transcription (RT)-PCR to detect RNA processing abnormalities; (3) semi-quantitative PCR using capillary electrophoresis to detect large heterozygous deletions. Using the three-step analysis, we identified homozygous or compound heterozygous mutations in all patients. Interestingly, 20 % of our ARAS patients showed normal expression of α5 in kidney tissue. The median age of developing end-stage renal disease was 21 years. The strategy described in this study improves the diagnosis for ARAS families. Although immunohistochemical analysis of α5 can provide diagnostic information, normal distribution does not exclude the diagnosis of ARAS.
    Pediatric Nephrology 03/2014; 29(9). DOI:10.1007/s00467-014-2797-4 · 2.88 Impact Factor
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    ABSTRACT: Background Alport syndrome is a progressive inherited glomerulonephritis leading to renal failure, hearing loss and ocular changes. Purpose To report the seventh case of giant macular hole in a patient with Alport syndrome, review the literature, and propose a pathophysiological mechanism. Methods The case of a man with a giant macular hole of the right eye is described with visual acuity, fundus photographs and spectral domain ocular coherence tomography. Results A 56-year-old man with Alport syndrome and giant macular hole (2291 μm × 2265 μm) in his right eye, reducing the visual acuity to 20/200, complained of progressive visual loss in his contralateral eye. Fundus examination of the left eye revealed a circular perimacular atrophy. Conclusion Giant macular holes are one possible retinal complication of Alport syndrome. Their pathogenesis differs from idiopathic macular holes and may result from the combination of collagen type IV abnormalities in the basement membranes of both Bruch's membrane and the internal limiting membrane, along with anomalous vitreo-retinal adhesion.
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