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Saudi Journal of Kidney Diseases and Transplantation
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LETTER TO THE EDITOR Table of Contents   
Year : 2009  |  Volume : 20  |  Issue : 6  |  Page : 1087-1089
Alport's syndrome

1 Department of Internal Medicine, College of Health Sciences, Niger-Delta University, Bayelsa State, Nigeria
2 Department of Anatomy, School of Basic Medical Sciences, College of Medical Sciences,University of Benin, Benin City, Benin
3 Department of Anatomy, School of Basic Medical Sciences,College of Health Sciences, Delta State University, Abraka, Nigeria
4 Department of Clinical Sciences, College of Health Sciences, Niger Delta University, Amassoma, Bayelsa State, Nigeria

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Date of Web Publication27-Oct-2009

How to cite this article:
Oni AO, Eweka AO, Otuaga PO, Odia JO. Alport's syndrome . Saudi J Kidney Dis Transpl 2009;20:1087-9

How to cite this URL:
Oni AO, Eweka AO, Otuaga PO, Odia JO. Alport's syndrome . Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2022 Sep 25];20:1087-9. Available from: https://www.sjkdt.org/text.asp?2009/20/6/1087/57273
To the Editor,

Alport's syndrome encompasses a group of heterogeneous inherited disorders involving the basement membranes of the kidney and fre­quently involves the cochlea and the eye. [4],[5] These disorders are the result of mutations in 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 basement membranes in the kidney, inner ear, and eye. The 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 normally, allowing blood and protein into the urine. The abnormalities of type IV collagen in kidney basement membranes cause gradual scarring of the kidneys, eventually leading to kidney failure in many people with the disease. [1],[2],[3],[6] The mode of inheritance is X-linked in 80%, autosomal recessive in 15%, and auto­somal dominant is reported in about 5% of indi­viduals with Alport's syndrome. [1],[2],[7]

Children with Alport's syndrome may initially present with only persistent hematuria and/or a family history of hematuria. Auditory or ocular manifestations may appear later in life. The typi­cal changes of the glomerular basement mem­brane (GBM) are also age-dependent and may be absent from initial biopsy samples obtained from young children with Alport's syndrome. [8]

Alport's syndrome, also known as Dickinson's syndrome is a composite of renal, eye and ear disorders. [6],[9],[10],[11],[12] Platelet disorders and leio­myomatosis, which usually involves hollow organs like the trachea, esophagus and the female genital tract have also been described. [12],[13]

The incidence of Alport's syndrome is about 1 in 5000 in the general population. [14],[15] Normally, the GBM mostly contains the tissue specific X3, X4, X5 chains of type IV collagen. How­ever, in Alport's syndrome, this network is dis­rupted and replaced by X1 and X2 chains. [15],[16] As a result, the GBM which appears structu­rally normal in early life becomes thin with time. [15] It may later progress to thickening of the GBM which later undergoes the process of spli­tting and then degeneration. On light micros­copy, renal histologic findings are nonspecific and might not be observed in early Alport's syndrome. With progression, increased mesan­gial matrix, segmental proliferation, and seg­mental sclerosis may appear. [11],[17]

Electron microscopy reveals the characteristic lesions of Alport's syndrome; the GBM is irre­gularly thickened. The central lamina densa is split and splintered into a heterogeneous net­work of strands, which enclose electron-lucent areas that may contain microgranulations. The epithelial aspect of the capillary wall is irregular, and epithelial foot processes are fused. Thicke­ning of the GBM is usually diffuse in adults with Alport's syndrome, but in young children with the disorder, the thickening is segmental, and thinning of the basement membrane may be observed or even predominate. The degree of thickening increases with the patient's age and the degree of proteinuria. Therefore, a thick and split GBM is specific for Alport's syndrome; however, its absence does not exclude the syn­drome, especially in young children. [17]

The basement membranes can be immuno­histochemically evaluated by using monoclonal antibodies directed against the a3, a4, and a5 chains of type IV collagen. The absence of these chains in the GBM is characteristic of Alport's syndrome. Because the a5 chain is also expressed in the epidermal basement membrane, skin biopsy is an additional tool for diagnosis. Male patients with X-linked Alport's syndrome have a complete absence of a3, a4, and a5 chains in the glomerular and epithelial basement mem­branes, whereas female patients with X-linked disease have mosaicism and segmental loss of staining. [17],[18] In patients with the autosomal re­cessive variety, the GBM demonstrates no ex­pression of the a3, a4, and a5 chains, but expre­ssion of the a5 chain is present in the epidermal basement membrane. [9],[18],[19]

Management of Alport's syndrome involves making correct diagnosis and treatment of com­plications. Slit lamp examination of the lens shows bilateral anterior lenticonus. Audiogram of the affected ears will reveal sensorineural deafness to high tone sound initially. [20],[21] Renal ultrasound will show bilateral shrunken kidneys. There may be impaired renal functions. Treat­ment includes the control of hypertension and prescribing of hearing aids. If a patient is in re­nal failure, dialysis is advised. End-stage renal disease is treated with renal transplant. [22] The case presented below is, to our knowledge, the first reported case from the Niger Delta region (Bayelsa State) of Nigeria.

AA is a 57-year-old male retired civil servant, who presented to the medical outpatient de­partment of the Niger Delta University Teaching Hospital for management of poorly treated hy­pertension. Past medical history revealed that the patient had difficulty in passing urine from childhood. There was also a history of gradual sight deterioration from childhood and hearing loss at the age of 22 years. There was no similar history of sight and hearing defect in any of the family members. Physical examination re­vealed persistently elevated blood pressure, fixed right pupil and sluggish reaction of left pupil to light. Both discs were pale bilaterally. There was nystagmus, glaucoma, bilateral anterior lenti­conus and proptosis. Audiogram examination of the ears demonstrated a sensorineural deafness for which hearing aid had been prescribed. Renal ultrasonography showed bilateral shrun­ken kidneys with loss of corticomedullary diffe­rentiation (right kidney 7.0 Χ 3.3 cm and left kidney 7.4 Χ 4.4 cm). The blood urea and serum creatinine levels were slightly elevated. Urina­lysis showed trace of proteinuria and microhema­turia. Urine culture did not yield any bacterial growth and the glomerular filtration rate was 86 mL/min. Kidney biopsy was not done because the kidney size was small. His blood pressure was controlled with nifedipine and duretics.

This case report has brought to focus the po­ssibility of a spontaneous genetic mutation of Alport's syndrome. Autosomal dominant inheri­tance is possible, [23] in which case, heterozygous carriers of the gene will always have the disease irrespective of sex. However, spontaneous ge­netic mutations have also been described in some people who may have no family history of Alport's syndrome. [14],[16] This seems to be the case in our patient who had no family history of Alport's syndrome.

Our patient had glaucoma, nystagmus, optic atrophy, bilateral anterior lenticonus and prop­tosis. Glaucoma is not a usual ocular presen­tation in Alport's syndrome. [10],[24] There was no appreciable improvement in the sight and hea­ring of this patient. He had not purchased his hearing aids owing to financial difficulties. Apart from the control of hypertension, the use of hearing aids, renal dialysis and renal trans­plant, there is no known treatment. However, gene therapy for Alport's syndrome is being studied. Animal studies are underway to eva­luate the use of human alpha (iv) chain of GBM in a canine model of x-linked Alport's syndro­me. [25]

Our case re-emphasizes the need for complete renal investigation in cases of childhood or adult visual impairment and hearing loss, or vice-versa.

   References Top

1.Anker MC, Arnemann J, Neumann K, et al. Alport syndrome with diffuse leiomyoma­tosis. Am J Med Genet A 2003;119(3):381-5.  Back to cited text no. 1      
2.Kashtan CE, Michael AF. "Alport syndrome". Kidney Int 1996;50(5):1445-63.  Back to cited text no. 2      
3.Tryggvason K, Heikkila P, Pettersson E, Tibell A, Thorner P. Can Alport syndrome be treated by gene therapy? Kidney Int 1997;51(5):1493-9.  Back to cited text no. 3      
4.Flinter F. Alport's Syndrome. J Med Genet 1997;34(4):326-30  Back to cited text no. 4      
5.Paul ST. Alports Syndrome and thin glomerular basement membrane nephropathy. Clin Pract 2007;106(2):1-7  Back to cited text no. 5      
6.Kashtan CE. Familial hematuria due to type IV collagen mutations: Alport syndrome and thin basement membrane nephropathy. Curr Opin Pediatr 2004;16(2):177-81.  Back to cited text no. 6      
7.Gregory MC, Terreros DA, Barker DF, Fain PN, Denison JC, Atkin CL. Alport syndrome-­clinical phenotypes, incidence, and pathology. Contrib Nephrol 1996;117:1-28.  Back to cited text no. 7  [PUBMED]    
8.Copelovitch L, Kaplan BS. Is genetic testing of healthy pre-symptomatic children with possible Alport syndrome ethical? Pediatr Nephrol 2006; 21(4):455-6  Back to cited text no. 8      
9.Nagel M, Nagorka S, Gross O. Novel COL4­A5,COL4A4,COL4A3 mutations in Alport's syndrome. Hum Mutat 2005;26(1):60.  Back to cited text no. 9      
10.Colville OJ, Savige J. Alport's syndrome. A review of the ocular manifestations. Ophthalmic Genet 1997;18(4):161-73  Back to cited text no. 10      
11.Sado Y, Kagawa M, Naito. Organization and expression of basement membrane collagen IV genes and their roles in human disorders. J Biochem 1998;123(5):767-76.  Back to cited text no. 11      
12.Grawfurd MA. Alports syndrome. J Med Genet 1988;25:623-7  Back to cited text no. 12      
13.Dong F, Li S, Pujol-Moix N, et al. Genotype­phenotype correlation in MYH9-related throm­bocytopenia. Br J Haematol 2005;130(4):620-7.  Back to cited text no. 13      
14.Heidet L, Cai Y, Gnicharnaud L. Glomerular expression of type IV collagen chains in normal an X-linked Aport's syndrome kidneys. Am J Pathol 2000;156(6):1901-10.  Back to cited text no. 14      
15.White RH, Raafat F, Milford DV. The Alport's nephropathy. Clinical pathological correlations. Pediatr Nephrol 2005;20(7):897-903.  Back to cited text no. 15      
16.Longo I, Scala E, Mari F. Autosomal recessive Alport's syndrome. Nephrol Dial Transplant 2006; 21(3):665-71.  Back to cited text no. 16      
17.Mazzucco G, Barsotti P, Muda AO, et al. Ultra­structural and immunohistochemical findings in Alport''s syndrome: a study of 108 patients from 97 Italian families with particular emphasis on COL4A5 gene mutation correlations. J Am Soc Nephrol 1998;9(6):1023-31.  Back to cited text no. 17      
18.Meloni I, Muscettola M, Raynaud M, et al. FA­CL4, encoding fatty acid-CoA ligase 4, is mu­tated in nonspecific X-linked mental retardation. Nat Genet 2002;30(4):436-40.  Back to cited text no. 18      
19.Meloni I, Vitelli F, Pucci L, et al. Alport syn­drome and mental retardation: clinical and ge­netic dissection of the contiguous gene deletion syndrome in Xq22.3 (ATS-MR). J Med Genet 2002;39(5):359-65..  Back to cited text no. 19      
20.Lemmink HH, Schroder CH, Monnens LA. The clinical spectrum of type IV collagen mutations. Hum Mutat 1997;9(6):477-99.  Back to cited text no. 20      
21.Kashtan CE. Diagnosis of Alports syndrome. Kidney Int 2004;66:1290-1  Back to cited text no. 21  [PUBMED]  [FULLTEXT]  
22.Pirson Y. Making the diagnosis of Alport's syndrome. Kidney Int 1999;56(2):760-75.  Back to cited text no. 22      
23.Kharr M, Makni S, Makni K, et al. Autosomal dominant Alports syndrome. Saudi J Kid Dis Transpl 2006;17(3):320-5.  Back to cited text no. 23      
24.Swann PG, Patel S. Lenticular changes in Al­port's syndrome. Clin Exp Optom 2005;88(1): 53-4.  Back to cited text no. 24      
25.Heikkila P, Tryggvason K, Thorner P. Animal model of Alport's syndrome. Advancing the prospects for effective human gene therapy. Exp Nephrol 2000;8(1):1-7.  Back to cited text no. 25      

Correspondence Address:
Andrew Osayame Eweka
Department of Anatomy, School of Basic Medical Sciences, College of Medical Sciences,University of Benin, Benin City
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Source of Support: None, Conflict of Interest: None

PMID: 19861880

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