Saudi Journal of Kidney Diseases and Transplantation

: 2011  |  Volume : 22  |  Issue : 6  |  Page : 1238--1239

Presentation of seven members of a family with the Alport's syndrome

Ymer Elezi, Blerta Rugova, Arjeta Hasani, Erblin Elezi, Bejtush Zylfiu, Skender Telaku, Ibrahim Rrudhani 
 Department of Nephrology and Hemodialysis, University Clinical Center of Kosova, 10,000 Pristina, Republic of Kosovo

Correspondence Address:
Ymer Elezi
Department of Nephrology and Hemodialysis, University Clinical Center of Kosova, 10,000 Pristina
Republic of Kosovo

How to cite this article:
Elezi Y, Rugova B, Hasani A, Elezi E, Zylfiu B, Telaku S, Rrudhani I. Presentation of seven members of a family with the Alport's syndrome.Saudi J Kidney Dis Transpl 2011;22:1238-1239

How to cite this URL:
Elezi Y, Rugova B, Hasani A, Elezi E, Zylfiu B, Telaku S, Rrudhani I. Presentation of seven members of a family with the Alport's syndrome. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2022 Oct 7 ];22:1238-1239
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Full Text

To the Editor

Alport's Syndrome (AS) is a rare hereditary kidney disease characterized by the presence of hematuria with progressive renal failure, sensory neural hearing loss and with several ocular abnormalities. The syndrome was first described by Dr. Cecil A. Alport in a British family in 1927. [1],[2] Males are more severely affected than females. Frequency of appearance in the overall population is around one in 10,000 inhabitants. The AS is caused by mutation in COL 4A3, 4A4 and 4A5. We report on a family in Kosovo in which several members had AS.

Three brothers and a sister, all from a single region in Kosova, presented within short intervals with features of chronic renal disease. All of them had associated hearing and visual abnormalities. Subsequently, after laboratory analysis and kidney biopsy, the diagnosis of AS was established. Because of worsening of their renal function, two of the brothers had to be started on hemodialysis (HD) treatment abroad. Both died due to complications related to the cardiovascular system. The third brother is currently on chronic HD abroad and is in the waiting list for kidney transplantation.

The only sister from this family was started on chronic HD at the age of 60 years. Of these four children, the older son and the only daughter have undergone renal transplantation abroad. The middle son has been on chronic HD for two years. Only the younger son, currently aged 23 years, has neither clinical nor biochemical features of AS.

The first features noticed in these patients were loss of hearing, micro-hematuria, anemia and hypertension [Table 1]. The anemia was treated with the use of erythropoietin while the hypertension was treated with ACE inhibitors. In patients with high proteinuria, a decrease of the same and reduction of the rate of progression of the renal disease was noticed after the use of ACE inhibitors. Thus, the use of ACE inhibitors is recommended in patients with the AS. [3]{Table 1}

Thrombocytopenia was a characteristic feature among all patients. Two patients had repeated subcutaneous bleeding and epistaxis. In all cases, impaired hearing was more severe compared with the impairment of vision. However, the problems with vision were more severe in females. Ultrasound of the kidneys showed contracted and sclerotic kidneys. In two of the seven members of this family, biopsy of the kidney was performed. Light microscopy showed mesangial cellular proliferation with progresssive glomerular sclerosis. Electron microscopy showed diffuse thickening and splitting of the basal membrane in both patients.

Gregory et al in 1966 laid down ten criteria for the clinical diagnosis of AS. [4] AS is more frequently seen in men than in women. The autosomal-recessive pattern of inheritance is seen in around 15%, while the dominant pattern is seen in approximately 1% of the cases. [2]

The occurrence of AS in a family is being reported for the first time from Kosovo. Predominance of thrombocytopenia, hearing abnormalities and micro-hematuria, enabled us to make a diagnosis of AS in this family; [5] this trait is generally seen in the autosomal-dominant type. However, we were unable to perform genetic study of this family in order to specify, exactly, the kind of mutations present in these patients. It is known that up to 100 mutations, including missense mutations, splice-site mutations and small deletions, account for most cases of X-linked AS. Often, up to 80% of the patients with X-linked AS have mutations in the COL4A5 gene. However, the most common mutation involves substitution of glycine in the collagenous domain of the a5 (IV) chain by a bulky amino acid, resulting in protein-folding abnormalities. Peculiarly, patients with autosomal-dominant AS also have heterozygous mutations in the COL4A3 and COL4A4 genes.

Male members of this family showed their first disease symptoms after the age of 20 years, with the age at commencement of HD being between 25 and 30 years. Among females, the children's mother was started on HD at the age of 60 years, while her daughter was initiated on HD at the age of 30 years. Thus, in our patients, the development of the disease process was earlier in men than in women.

The AS is caused by mutation of the gene for biosynthesis of collagen 4A3, 4A4 and 4A5. This kind of collagen is a very important structural component of the basement membrane. In our series, progression of the renal disease was much quicker in men than in women. Microhematuria, thrombocytopenia and abnormalities in hearing were the earliest features of the disease. All the study patients ended up on HD, while two of them underwent renal transplantation.


1Alport AC. Hereditary familial congenital haemorrhagic nephritis. Br Med J 1927;1:504-6.
2Gregory MC, Terreros DA, Barker DF, Fain PN, Denison JC, Atkin CL. Alport Syndrome-Clinical fenotypes and pathology: Contrib. Nephrol 1995;117:1-28.
3Epstein CJ, Sahud MA, Piel CF, et al. Hereditary macrothrombocitopathia nephritis and deafness. Am J Med 1972;52(3):299-310.
4Remuzzi A, Fassi A, Bertoni T, et al. ACE inhibition induces regression of proteinuria and halts progression of renal damage in a genetic model of progressive nephropaty. Am J Kidney Dis 1999;34(4):626-32 (Abstract).
5Lagona E, Tsartsali L, Kostaridon S, Sriathitoy A, Georgaki E, Satson F. (April 2008) Skin biopsy for the diagnosis of Alport Syndrome. Hippokratia 2008;12(2):116-8.