Hereditary Nephritis and Thin Glomerular Basement Membrane Lesion

Lusco, Mark A.; Fogo, Agnes B.

doi:10.1159/000516744

Cited by 3 publications

(3 citation statements)

References 28 publications

(41 reference statements)

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“…The routine immunofluorescence panel typically shows no immune complex deposits. Electron microscopic studies are heterogenous and can show thin glomerular basement membrane lesion alone or variable amounts of atypical glomerular basement membrane remodeling (e.g., lamina densa splitting, basket weave pattern lamina densa remolding, and subepithelial scalloping) [ 21 ]. The presence of any of these electron microscopic findings should trigger considerations for genetic studies.…”

Section: Discussionmentioning

confidence: 99%

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Sporadic Case of Heterozygous X-Linked Alport Syndrome

Zuckerman¹,

Srivastava²

2023

Glomerular Dis

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Alport syndrome is a genetically and phenotypically heterogeneous disorder that can be transmitted in an X-linked, autosomal recessive, or autosomal dominant fashion and can affect glomerular, cochlear, and ocular basement membranes. The disorder results from mutations in the collagen IV genes COL4A5 (X chromosome), COL4A3, and COL4A4. Alport patients are at lifetime risk for kidney failure, sensorineural deafness, and ocular abnormalities. Males with Alport syndrome typically present with severe phenotype with progression to end-stage kidney disease and/or sensorineural deafness and eye changes. Females generally having less severe presentation and diagnosis of X-linked Alport syndrome are generally not considered. Here, we report a case of a 3-year-old girl with gross hematuria, proteinuria, and chronic kidney disease who was found to have features of Alport syndrome on kidney biopsy and a sporadic heterozygous pathogenic COL4A5 deletion on molecular testing. This case report emphasizes the importance of kidney biopsy and molecular testing in the work up of pediatric patients with hematuria, proteinuria, and/or chronic kidney disease. It is also a poignant illustration that females with heterozygous X-linked COL4A5 mutations are often affected patients. It further illustrates the phenomenon of sporadic occurrence of genetic kidney disease in the absence of family history of kidney disease.

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Section: Discussionmentioning

confidence: 99%

“…Typically, we defer directly to genetic studies with any suspicious biopsy findings as this will generally provide a definitive diagnosis with the most prognostic information. Furthermore, genetic studies also are important to rule out the rare biopsy mimics of Alport syndrome including, LMX1B , LAMB2 , and WT-1 mutations [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Sporadic Case of Heterozygous X-Linked Alport Syndrome

Zuckerman¹,

Srivastava²

2023

Glomerular Dis

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“…5,6 TBMN, also known as benign familial hematuria, affects about 1% of the general population. [7][8][9] Approximately 50% of patients with TBMN present as an autosomal dominant pattern, and 40-50% as mutations in the COL4A3 or COL4A4 genes on the X chromosome. 10 These mutations cause slight reductions in the length of the α3α4α5 network in collagen type IV of the GBM, unlike AS, where type IV collagen networks are destroyed or deformed severely.…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological Features of Hereditary Nephritis in the Iranian Population: Analysis of a 14-Year Survey in Kidney Biopsies From a Large Referral Center

Emami,

Nili,

Sotoudeh Anvari

et al. 2024

Arch Iran Med

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Background: Hereditary nephritis (HN), including Alport syndrome (AS) and thin basement membrane nephropathy (TBMN), is a rare genetic cause of hematuria. A definitive diagnosis requires electron microscopy (EM). Therefore, the clinical characteristics of these conditions are less known. This study aimed to determine the percentage and clinicopathological features of HN in patients from a referral center in Iran. Methods: We checked kidney biopsy reports from 2007 to 2021 and extracted cases with HN. Fresh specimens of the cases diagnosed in the last two years were stained by immunofluorescence (IF) for collagen type IV alpha chains. EM findings in these cases were re-evaluated and categorized as diffuse glomerular basement membrane (GBM) thinning, definite, and suspicious features of AS. Results: We analyzed 3884 pathology reports of kidney biopsies from 2007 to 2021 and identified 210 patients (5.4%) with HN, with a mean age of 13.78±12.42 years old. Hematuria with proteinuria (53.3%), isolated hematuria (44.2%), and proteinuria with hematuria and increased creatinine (2.5%) were found in these patients. The re-evaluation of EM findings revealed GBM thinning, definite, and suspicious findings of AS in 37.5%, 43.8%, and 18.8% cases, respectively. The most common diagnosis in 32 cases after the IF study was X-linked AS (71.9%), and 6.2% of cases were autosomal recessive AS. TBMN and autosomal dominant AS remained the differential diagnoses in 21.9%. Conclusion: It was found that EM is helpful for the primary diagnosis of patients with definite AS. Immunostaining improves the diagnostic sensitivity for the differentiation of those with suspicious EM findings and determines the inheritance pattern. However, a multidisciplinary approach for a subset of cases is required for the best diagnosis and management.

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