scholarly journals Prevalence of clinical, pathological and molecular features of glomerular basement membrane nephropathy caused by COL4A3 or COL4A4 mutations: a systematic review

2020 ◽  
Vol 13 (6) ◽  
pp. 1025-1036 ◽  
Author(s):  
Andreas Matthaiou ◽  
Tsielestina Poulli ◽  
Constantinos Deltas
Keyword(s):  
Basement Membrane ◽  
Alport Syndrome ◽  
Autosomal Dominant ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Histological Finding ◽  
Basement Membranes ◽  
Thin Basement Membrane Nephropathy ◽  
Molecular Features ◽  
Thin Basement Membrane Disease

Abstract Background Patients heterozygous for COL4A3 or COL4A4 mutations show a wide spectrum of disease, extending from familial isolated microscopic haematuria, as a result of thin basement membranes (TBMs), to autosomal dominant Alport syndrome (ADAS) and end-stage renal disease (ESRD). Many patients are mentioned in the literature under the descriptive diagnosis of TBM nephropathy (TBMN), in which case it actually describes a histological finding that represents the carriers of autosomal recessive Alport syndrome (ARAS), a severe glomerulopathy, as most patients reach ESRD at a mean age of 25 years. Methods We performed a systematic literature review for patients with heterozygous COL4A3/A4 mutations with the aim of recording the spectrum and frequency of pathological features. We searched three databases (PubMed, Embase and Scopus) using the keywords ‘Autosomal Dominant Alport Syndrome’ OR ‘Thin Basement Membrane Disease’ OR ‘Thin Basement Membrane Nephropathy’. We identified 48 publications reporting on 777 patients from 258 families. Results In total, 29% of the patients developed chronic kidney disease (CKD) and 15.1% reached ESRD at a mean age of 52.8 years. Extrarenal features and typical Alport syndrome (AS) findings had a low prevalence in patients as follows: hearing loss, 16%; ocular lesions, 3%; basement membrane thickening, 18.4%; and podocyte foot process effacement, 6.9%. Data for 76 patients from 54 families emphasize extensive inter- and intrafamilial heterogeneity, with age at onset of ESRD ranging between 21 and 84 years (mean 52.8). Conclusions The analysis enabled a comparison of the clinical course of patients with typical ARAS or X-linked AS with those with heterozygous COL4A mutations diagnosed with TBMN or ADAS. Despite the consequence of a potential ascertainment bias, an important outcome is that TBM poses a global high risk of developing severe CKD, over a long follow-up, with a variable spectrum of other findings. The results are useful to practicing nephrologists for better evaluation of patients.

scholarly journals How genomics reclassifies diseases: the case of Alport syndrome

2020 ◽  
Vol 13 (6) ◽  
pp. 933-935 ◽  
Author(s):  
Roser Torra ◽  
Monica Furlano ◽  
Elisabet Ars
Keyword(s):  
Basement Membrane ◽  
Alport Syndrome ◽  
Autosomal Dominant ◽  
Wide Spectrum ◽  
Unknown Origin ◽  
Thin Basement Membrane Nephropathy ◽  
Pathogenic Variants ◽  
Thin Basement Membrane Disease ◽  
Extreme Phenotypes ◽  
Generation Sequencing

Abstract In this issue, Matthews et al. provide a comprehensive review of published cohorts with heterozygous pathogenic variants in COL4A3 or COL4A4, documenting the wide spectrum of the disease. Due to the extreme phenotypes that patients with heterozygous pathogenic variants in COL4A3 or COL4A4 may show, the disease has been referred to in a variety of ways, including ‘autosomal dominant Alport syndrome’, ‘thin basement membrane disease’, ‘thin basement membrane nephropathy’, ‘familial benign hematuria’ and ‘carriers of autosomal dominant Alport syndrome’. This confusion over terminology has prevented nephrologists from being sufficiently aware of the relevance of the entity. Nowadays, however, next-generation sequencing facilitates the diagnosis and it is becoming a relatively frequent finding in haematuric–proteinuric nephropathies of unknown origin, even in non-familial cases. There is a need to raise awareness among nephrologists about the disease in order to improve diagnosis and provide better management for these patients.

scholarly journals The Genetics, Current Research, and Future Treatment of Alport Syndrome

2017 ◽  
Vol 6 (1) ◽  
pp. 1-7
Author(s):  
Elise Alexandra Kikis ◽  
Emily Holland Williams
Keyword(s):  
Basement Membrane ◽  
End Stage Renal Disease ◽  
Alport Syndrome ◽  
Autosomal Recessive ◽  
Type Iv Collagen ◽  
Autosomal Dominant ◽  
Basement Membranes ◽  
Type Iv ◽  
Stage Renal Disease ◽  
End Stage

Alport syndrome is a type IV collagen disease that affects the glomerular basement membrane of approximately one in every 5000 people. The disease was first described by A. Cecil Alport in 1927 as “a dominantly inherited hereditary nephritis.” The three genotypes of the disease are X-linked dominant, autosomal recessive, and autosomal dominant. The X-linked dominant genotype is the most common, accounting for 80% of all cases of Alport syndrome, affecting mainly men. The autosomal recessive and autosomal dominant types affect men and women equally. Alport syndrome is caused by mutations on the COL4A3, COL4A4, and COL4A5 genes, which code the ?3, ?4, and ?5 (IV) chains that make up type IV collagen molecules, an important component of basement membranes. Thus, Alport syndrome results in malformed basement membranes, with symptoms including renal impairment, hematuria, bilateral sensorineural hearing loss, and an abnormal structure of the glomerular basement membrane. Alport syndrome also often progresses to end-stage renal disease, especially in men with X-linked Alport syndrome. At this point, there is no cure for Alport syndrome. However, there are many successful treatments for its symptoms. Angiotensin-converting enzyme (ACE) inhibitors are often given to patients in the early stages of Alport syndrome. For patients with end-stage renal disease, dialysis or kidney transplants are considered the best course of action.

A Novel Mutation of COL4A3 Presents a Different Contribution to Alport Syndrome and Thin Basement Membrane Nephropathy

2007 ◽  
Vol 27 (5) ◽  
pp. 538-544 ◽  
Author(s):  
Ping Hou ◽  
Yuqing Chen ◽  
Jiaxiang Ding ◽  
Guangtao Li ◽  
Hong Zhang
Keyword(s):  
Basement Membrane ◽  
Alport Syndrome ◽  
Novel Mutation ◽  
Thin Basement Membrane Nephropathy

scholarly journals Thin basement membrane disease – literature review

2015 ◽  
Vol 84 (3) ◽  
pp. 201-204
Author(s):  
Jakub Żurawski
Keyword(s):  
Electron Microscope ◽  
Basement Membrane ◽  
Literature Review ◽  
Iga Nephropathy ◽  
Glomerular Basement Membrane ◽  
Alport Syndrome ◽  
Clinical Course ◽  
Renal Diseases ◽  
Renal Lithiasis ◽  
Thin Basement Membrane Disease

Initially, the thin glomerular basement membrane disease was called “a gentle and curable hemorrhagic nephritis”. The thin basement membrane disease has been finally characterized at the beginning of 1970s. This is when the connection between previously clinically described gentle microhematuria and significant thinning of glomerular basement membrane discovered during examination under the electron-microscope has been established. Ultimately, the disease has been described as a condition characterized with a diverse clinical course, usually mild, but sometimes progressive. It is a family conditioned disease, but it also appears sporadically and concerns at least 1% of the population. It has also been stated that it is one of the most frequent renal diseases, enumerated directly after changes caused by infections, hypertension and renal lithiasis. This particular disease is diagnosed more often than IgA nephropathy and Alport syndrome, which are also associated with haematuria or microhematuria.

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