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Background
This is a rare inherited disease that chiefly affects the kidneys. It is caused by mutations in one or the other of several COL4A genes. These genes encode for the elements of the basement membrane (Type IV) collagen. The result is a hereditary glomerulonephritis with a chronic nephritis that progresses to end-stage renal disease. Associated conditions include hearing loss, lenticonus and other eye disorders, immunologic abnormality of skin, disorders of platelets, abnormalities of white blood cells, and smooth muscle tumors.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS X-linked hereditary nephritis INCIDENCE/PREVALENCE About 5000 individuals worldwide AGE SEX GEOGRAPHY CHINESE
Phenotypic and genotypic features of Alport syndrome in Chinese children.Wang F, Ding J, Guo S, Yang J.
Department of Pediatrics, First Hospital, Peking University, Beijing, China.
Pediatr Nephrol 2002 Dec;17(12):1013-20 Abstract quote Chinese Alport syndrome (AS) was analyzed in 44 unrelated patients who were screened for mutations in the COL4A5 gene by polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis or PCR direct sequencing in 30 of the 44 patients.
The clinical data showed that all patients had hematuria; 25 of 29 male patients (86%) and 9 of 15 female patients (60%) had proteinuria; 11 of 29 male patients (38%) and 1 of 15 female patients (7%) had nephrotic-level proteinuria; 10 of 21 male patients examined (48%) and 1 of 12 female patients examined (8%) had hearing abnormalities.
Renal function remained normal despite hearing abnormalities, and ocular lesions occurred in 10%. Among 30 of 44 patients who had a family history of end-stage renal disease (ESRD), 80% (24/30) belonged to X-linked juvenile kindreds, and 20% (6/30) patients to adult kindreds. Of the 44 patients, 14 did not have a family history of ESRD, while 11 of 14 patients diagnosed with X-linked AS did. DNA analysis revealed four missense mutations, two silent mutations, one substitution, and one in-frame deletion. PCR along with Southern hybridization analysis revealed a large deletion of the paired COL4A5 and COL4A6 genes.
Chinese AS patients were characterized clinically with hematuria, heavy proteinuria, and more juvenile forms. Mutations in these patients were usually small mutations, while a large deletion involving the 5' part of both COL4A5 and COL4A6 genes was identified.
DISEASE ASSOCIATIONS CHARACTERIZATION
PATHOGENESIS CHARACTERIZATION
LABORATORY/RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC LABORATORY MARKERS
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL VARIANTS
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE ELECTRON MICROSCOPY
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
PROGNOSIS CHARACTERIZATION
TREATMENT CHARACTERIZATION GENERAL CYCLOSPORINE
Cyclosporine a slows the progressive renal disease of alport syndrome (x-linked hereditary nephritis): results from a canine model.Chen D, Jefferson B, Harvey SJ, Zheng K, Gartley CJ, Jacobs RM, Thorner PS.
Divisions of Structural Biology and Biochemistry and Pathology, Hospital for Sick Children, Toronto, Canada.
J Am Soc Nephrol 2003 Mar;14(3):690-8 Abstract quote ABSTRACT. Alport syndrome refers to a hereditary disorder characterized by progressive renal disease and a multilaminar appearance to the glomerular basement membrane (GBM). In a small group of patients with Alport syndrome, cyclosporine A was reported to decrease proteinuria and maintain stable renal function over 7 to 10 yr of follow-up.
The present study examined the effect of cyclosporine A on GBM structure and the progression to renal failure in a canine model of X-linked Alport syndrome. Affected male dogs and normal male dogs treated with cyclosporine A underwent serial renal biopsies. Body weight, serum concentrations of creatinine and albumin, and GFR were sequentially determined. Controls consisted of untreated dogs that developed end-stage renal failure by 8 mo of age.
Renal biopsies were assessed for glomerulosclerosis and the percent of multilaminar GBM as measured by image analysis. Significant differences were found between treated and untreated affected dogs for weight, serum creatinine, and GFR. There was a significant delay in the progression of multilaminar change to the GBM, although treated affected dogs at termination had attained approximately 100% split GBM as did untreated affected dogs. A significant difference in the number of sclerotic glomeruli was also noted; treated dogs rarely developed obsolete glomeruli during the period studied. Interstitial fibrosis was not significantly affected by cyclosporine A treatment.
These findings indicate that cyclosporine A is beneficial in slowing, but not stopping, the clinical and pathologic progression of Alport syndrome. At least part of this beneficial effect comes from a delayed deterioration of GBM structure, which in turn may be related to glomerular hemodynamics altered by cyclosporine A.
RENAL TRANSPLANT
Renal transplant in patients with Alport's syndrome.Byrne MC, Budisavljevic MN, Fan Z, Self SE, Ploth DW.
Department of Biometry, Nephrology Division, Medical University of South Carolina, Charleston, SC 29425, USA.
Am J Kidney Dis 2002 Apr;39(4):769-75 Abstract quote We evaluated 52 renal grafts transplanted into 41 patients with a pretransplantation diagnosis of Alport's syndrome. Overall 1-, 5-, and 10-year patient and graft survival rates were 95.1%, 90.2%, and 80.5% and 86.8%, 66%, and 45.3%, respectively. Although 14% of renal graft biopsy specimens examined with immunofluorescent microscopy showed linear glomerular basement membrane (GBM) immunoglobulin G deposits, only 1 of 41 patients (2.4%) or 52 grafts (1.9%) developed posttransplantation anti-GBM disease.
The incidence of anti-GBM disease was 3.1% (1 of 32 patients) in a subgroup of male transplant recipients. Our analysis suggests that the incidence of anti-GBM disease in transplant recipients with Alport's syndrome is less than previously reported. In addition, it does not appear that HLA-DR alleles, which predispose to the development of anti-GBM disease in native kidneys, have a role in transplant recipients with Alport's syndrome posttransplantation. However, immunosuppression level may have a pathophysiological role in the development of anti-GBM disease.
The majority of grafts in transplant recipients with Alport's syndrome failed because of chronic allograft nephropathy (69% of grafts) and acute rejection (22% of grafts). A history of previous acute rejection was the only factor that significantly affected graft outcome.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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Last Updated 1/20/2003
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