1/22. Sporadic case of X-chromosomal Alport syndrome in a consanguineous family.Alport syndrome (AS) is a genetic disorder of basement membranes caused by mutations in type IV collagen genes that is characterized by chronic hematuria and progressive nephropathy leading to renal failure. The main extrarenal features include sensorineural hearing loss and ocular lesions. The mode of inheritance is X-linked dominant in about 80%-85% of the affected families, whereas autosomal transmission is rarely encountered. We report a male patient originating from a healthy consanguineous Lebanese family who presented with an unusual association of obstructive uropathy and AS. hematuria and proteinuria were initially attributed to a suspected poststreptococcal glomerulonephritis (GN) and high-grade subpelvic ureteral stenosis. Persistence of symptoms after medical treatment of poststreptococcal GN and surgical correction of obstructive uropathy finally led to renal biopsy. The observed ultrastructural changes of the glomerular basement membrane were typical for AS. Molecular genetic studies revealed a previously undescribed de novo mutation in the COL4A5 gene, excluding maternal heterozygotic carrier status. This case report emphasizes the importance of hereditary nephritis in the differential diagnosis of chronic hematuria, and demonstrates the value of molecular studies for genetic counselling in AS.- - - - - - - - - - ranking = 1keywords = glomerulonephritis (Clic here for more details about this article) |
2/22. Alport-like glomerular changes in a patient with nephrotic syndrome: report of a case.We report a 17-year-old Saudi girl who presented with nephrotic syndrome at the age of 7 years. A renal biopsy revealed a mildly proliferative immune complex-mediated glomerulonephritis, which on ultrastructural examination revealed prominent thickening of the capillary basement membranes, along with marked splitting and lamellation of lamina densa resembling those seen in Alport syndrome. These changes were even more pronounced in renal biopsies performed 1 and 3 years later, respectively. Thorough clinical evaluations and follow-up of more than 10 years failed to reveal any evidence of Alport syndrome. review of the literature revealed four similar cases reported previously. Diffuse and prominent Alport-like glomerular changes may rarely be seen in patients with nephrotic syndrome in the absence of Alport syndrome. Pathogenesis of these changes, however, remains to be understood.- - - - - - - - - - ranking = 1keywords = glomerulonephritis (Clic here for more details about this article) |
3/22. Alport syndrome-like basement membrane changes in frasier syndrome: an electron microscopy study.frasier syndrome (FS) is a rare disease characterized by male pseudohermaphroditism and slowly progressing nephropathy. FS originates from heterozygous mutation in the intron 9 splicing donor site of Wilms' tumor suppressor gene (WT1). Focal segmental glomerular sclerosis is common in FS, but there have not been so many detailed pathologic investigations. The authors examined the kidneys of 3 patients with FS. The results showed that nephropathy started as mesangial proliferative glomerulonephritis, and later a concomitant focal segmental lesion developed. In all cases, electron microscopy results showed widespread thinning, splitting, and lamellation of the glomerular basement membrane, which mimicked hereditary nephritis. Throughout adulthood, WT1 protein expresses on glomerular podocytes. Recent reports described that podocytes expressing WT1 play an important role in maintaining the glomerular basement membrane. Hereditary nephritis-like glomerular basement membrane findings in FS suggest that one of the important functions of podocytes is to form and maintain the glomerular basement membrane.- - - - - - - - - - ranking = 1keywords = glomerulonephritis (Clic here for more details about this article) |
4/22. Alport syndrome and diffuse leiomyomatosis: deletions in the 5' end of the COL4A5 collagen gene.Alport syndrome (AS) is an hereditary glomerulonephritis that is mainly inherited as a dominant X-linked trait. Structural abnormalities in the type IV collagen alpha 5 chain gene (COL4A5), which maps to Xq22, have recently been detected in several patients with AS. The association of AS with diffuse esophageal leiomyomatosis (DL) has been reported in 24 patients, most of them also suffering from congenital cataract. The mode of transmission and the location of the gene(s) involved in this association have not been elucidated. Southern blotting using cDNA probes spanning the whole COL4A5 and a 5' end COL4A5 genomic probe showed that three out of three patients with the DL-AS association had a deletion in the 5' part of the COL4A5 gene extending beyond its 5' end. This indicates that the same gene, COL4A5, is involved in classical AS and in DL-AS and that the transmission of DL-AS is X-linked dominant. These results also suggest that leiomyomatosis might be due to the alteration of a second gene involved in smooth muscle cell proliferation, which is located upstream of the COL4A5 gene, and that there might be a contiguous gene deletion syndrome, involving at least the genes coding for congenital cataract, DL and AS.- - - - - - - - - - ranking = 1keywords = glomerulonephritis (Clic here for more details about this article) |
5/22. Retransplantation in Alport post-transplant anti-GBM disease.BACKGROUND: Post transplant anti-glomerular basement membrane (GBM) disease affects up to 5% of patients with Alport's syndrome. Defects in the COL4A5 gene are responsible for most cases, and alpha 5(IV)NC1 is the usual target for alloantibodies. Gene deletions are more commonly associated with this complication than are point mutations. The disease is severe in renal allografts and nearly always results in graft loss. methods: Three cases of retransplantation in Alport's syndrome are described here in detail. All cases were started on immunosuppressive therapy early in the course of their disease and one patient (case 2) received pre-emptive anti-T-cell therapy (Campath IH). Anti-GBM antibodies in these cases were investigated by standard anti-GBM enzyme-linked immunosorbent assay (ELISA), by indirect immunofluorescence, and by Western blotting using collagenase-digested human GBM and recombinant type IV collagen NC1 domains made in insect cells. RESULTS: All cases showed early antibody and complement fixation to human GBM. Target alloantibodies were to alpha 5(IV)NC1 domain predominantly. Cases two and three gave negative results on standard ELISA for anti-GBM antibodies. Pathologic examination revealed crescentic glomerulonephritis, which was rapid in onset in case 1, blunted and less aggressive in case 3, and case 2 developed segmental necrosis without crescent formation. Neutrophilic infiltrates were an early feature in all 3 cases. All cases are compared with a review of all retransplanted cases in the literature. CONCLUSION: Alport anti-GBM disease is a severe disease in retransplanted patients. Anti-T-cell therapy seemed to modify the pathologic findings but did not prevent graft loss. Longer term plasma exchange and mycophenolate mofetil may attenuate the illness, but in these cases did not prevent graft loss. Western blotting detected alloantibodies to alpha 5(IV) NC1 domain and is more sensitive and specific for this disease than standard ELISAs.- - - - - - - - - - ranking = 1keywords = glomerulonephritis (Clic here for more details about this article) |
6/22. Familial IgA nephropathy associated with bilateral sensorineural deafness.Alport's syndrome is the most frequent disorder with familial nephritis and deafness, but other types of nephropathy have been occasionally associated with hereditary hearing loss. The familial occurrence of IgA nephropathy has been well documented. We report a family with hereditary, bilateral, sensorineural deafness spanning four generations. Three of five members with deafness had microscopic hematuria. Renal histology of the two deaf members undergoing biopsy showed mesangial glomerulonephritis with mesangial IgA deposits, without ultrastructural abnormalities of the glomerular basement membranes. Familial nephritis with deafness should not be equated with the diagnosis of Alport's syndrome.- - - - - - - - - - ranking = 1keywords = glomerulonephritis (Clic here for more details about this article) |
7/22. The pathogenesis of Alport syndrome involves type IV collagen molecules containing the alpha 3(IV) chain: evidence from anti-GBM nephritis after renal transplantation.Mutations in the COL4A5 collagen gene have been implicated as the primary defect in Alport syndrome, a heritable disorder characterized by sensorineural deafness and glomerulonephritis that progresses to end-stage renal failure. In the present study, the molecular nature of the defect in Alport glomerular basement membrane (GBM) was explored using anti-GBM alloantibodies (tissue-bound and circulating) produced in three Alport patients subsequent to renal transplantation. The alloantibodies bound to the alpha 3(IV)NC1 domain of type IV collagen and not to any other basement membrane component. In tissue sections, the alloantibodies bound specifically to peripheral GBM in normal kidney and the affected renal transplant but not to that of Alport kidney. These results establish that: the alpha 3 chain in type IV collagen molecules, the Goodpasture autoantigen, is the target alloantigen in post-transplant anti-GBM nephritis in patients with Alport syndrome, and that a molecular commonality exists in the pathogenesis of anti-GBM nephritis causing loss of renal allografts in patients with Alport syndrome and renal failure in patients with Goodpasture syndrome. These findings implicate: (1) defective assembly of type IV collagen molecules containing the alpha 3(IV) chain in Alport GBM; and (2) the existence of a mechanism linking the assembly of molecules containing the alpha 3(IV) chain with those containing the alpha 5(IV) chain.- - - - - - - - - - ranking = 1keywords = glomerulonephritis (Clic here for more details about this article) |
8/22. Outcome of thirty patients with Alport's syndrome after renal transplantation.Graft antiglomerular basement membrane nephritis in patients with Alport's syndrome (AS) is a unique complication related to the glomerular basement membrane (GBM) abnormality characteristic of the disease. Its prevalence and clinical significance however remain unknown. We used strict criteria of AS to select 30 patients (26 men, 4 women), aged 17 to 44 years (m: 27) in whom 35 grafts (30 first, 5 second) had been performed at our center between 1968 and 1988. Patient and graft survival were, respectively, 96 and 75% at 5 years, 77 and 42% at 10 years. graft survival and function, as well as the incidence of rejection episodes in the AS group were not different from those of a control group without AS, matched for age, sex, graft origin, and immunosuppressive regimen. Fifteen grafts were examined by immunofluorescence at least 3 months after TP: linear IgG deposits along GBM were present in 5 cases in the absence of signs of crescentic glomerulonephritis. Circulating anti-GBM antibodies detected in one of these cases 8 months post-TP had disappeared 24 months later. The presence of linear IgG did not seem to influence graft survival and function. We conclude: (1) the overall outcome of TP in AS patients does not differ from a control group without AS; (2) appearance of linear glomerular IgG is frequent but is not necessarily associated with a poor graft outcome; (3) the course of de novo graft anti-GBM disease may be benign; and (4) the aggressivity of the disease could be determined by the degree of immunosuppression and/or by the specificity of the anti-GBM antibodies.- - - - - - - - - - ranking = 1keywords = glomerulonephritis (Clic here for more details about this article) |
9/22. Recurrent allograft antiglomerular basement membrane glomerulonephritis in a patient with Alport's syndrome.A patient with Alport's syndrome and chronic renal failure received a cadaver kidney graft. Four months after the transplantation, he developed glomerulonephritis induced by anti-glomerular basement membrane (GBM) antibody. The graft failed, and the patient returned to haemodialysis. Twenty-two months later the patient received a second cadaver kidney graft. Ten months after the second transplant, he developed a recurrent anti-GBM glomerulonephritis. This observation suggests that anti-GBM disease can recur in a second transplanted kidney in a patient with Alport's syndrome.- - - - - - - - - - ranking = 6keywords = glomerulonephritis (Clic here for more details about this article) |
10/22. Failure of two subsequent renal grafts by anti-GBM glomerulonephritis in Alport's syndrome: case report and review of the literature.We describe a patient with Alport's syndrome who developed severe crescentic glomerulonephritis after each of two successive transplantations, leading to accelerated graft failure on both occasions. This complication occurred in the 7th postoperative month for the first transplant and in the immediate postoperative period for the second. Immunopathological studies of the second transplant demonstrated that the glomerular lesions were mediated by antiglomerular basement membrane (GBM) antibodies displaying the same pattern of reactivity as the MCA-Pl monoclonal antibody directed against the Good-pasture antigen. This observation indicates that the anti-GBM immunization induced by renal transplantation in some patients with Alport's syndrome may be responsible for recurrent graft failure.- - - - - - - - - - ranking = 5keywords = glomerulonephritis (Clic here for more details about this article) |
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