Alport Syndrome: An Overview of the Pathology
Asian Journal of Research in Nephrology, Volume 5, Issue 3,
Alport syndrome (AS), also known as hereditary nephrosis, is an X-linked genetic disease that predominantly affects type IV collagen mainly in the kidneys and the eyes. It primarily affects males, particularly children, and can be transmitted via autosomal dominant and recessive inheritance modes. It typically presents with a triad of kidney involvement (nephritis), sensorineural hearing loss (SNHL), and visual impairment. Diseases related to mutation of the gene of the X chromosome include leiomyomatosis and AMME complex. AMME Complex is an acronym for alport syndrome, Midface hypoplasia, Mental retardation, and Elliptocytosis.
All type IV collagen genes must undergo mutation for the disease to occur. The most commonly implicated genes are COL4A3, COL4A4, and rarely COL4A5. It is one of the three prevalent inherited kidney diseases. In addition to others like polycystic kidney disease, cystinosis, Lowe syndrome, hereditary interstitial kidney disease, fabry disease, gittleman & barter's syndrome, and nephronophthisis.AS is considered a congenital disease.
The disease has no cure. Therapeutic strategies involve combating the symptoms and complications associated with the disease. The era of 21st-century technological evolution has clarified the diagnosis and evaluation of AS, but more studies are essential to help further understand the disease spectrum. This review article highlights the salient learning objectives to foster a better understanding of Alport syndrome for basic medical students and health professionals.
- Alport syndrome
- COL4A3-5 genes
- type IV collagen
- x-linked disorder
- chronic renal failure
How to Cite
Walead Latif. Nephrologist and clinical associate professor, rutgers medical school, newark, NJ. Review provided by VeriMed Healthcare Network 22; 2021. Alport syndrome (adam.com)
MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2020 June 24]. Alport syndrome, Genetics, [updated December 1; 2013.
cited 2022 August 16]-Alport syndrome: MedlinePlus Genetics
National Organization for Rare Disorders. NORD Compendium of Rare Diseases and Disorders. Acknowledgment of Clifford Kashtan, MD, FASN, Division of Pediatric Nephrology, Department of Pediatrics, University of Minnesota Medical School; Executive Director, Alport Syndrome Treatments and Outcomes Registry. Alport syndrome. February 13, 2020-Alport Syndrome - NORD (National Organization for Rare Disorders) (rarediseases.org)
BioNews Services, LLC. Alport syndrome News: Prevalence of Alport syndrome; 2013-2022.
Michael Gibson C, Aarti Narayan, Tarek Nafee, Shankar Kumar, Daniel Nethala, Raviteja Reddy Guddeti. Alport syndrome- WikiDoc; 2016.
Expert reviewer(s): Dr. Laurence HEIDET, Pr Rachel LENNON- Orphanet: Alport syndrome; 2020.
Slajpah M, Gorinsek B, Berginc G, Vizjak A, Ferluga D, Hvala A, Meglic A, Jaksa I, Furlan P, Gregoric A, Kaplan-Pavlovcic S, Ravnik-Glavac M, Glavac D. Sixteen novel mutations identified in COL4A3, COL4A4, and COL4A5 genes in Slovenian families with Alport syndrome and benign familial hematuria. Kidney Int. 2007;71(12): 1287-95.
Epub 2007 March 28.Alport Syndrome | National Kidney Foundation
Kashtan CE. Alport syndrome: an inherited disorder of renal, ocular, and cochlear basement membranes. Medicine.. Alport syndrome. An inherited disorder of renal, ocular, and cochlear basement membranes - PubMed (nih.gov) 1999; 78:338-60
Distribution of type IV collagen in the cochlea in Alport syndrome - PubMed (nih.gov) Zehnder AF, Adams JC, Santi PA, Kristiansen AG, Wacharasindhu C, Mann S, Kalluri R, Gregory MC, Kashtan CE, Merchant SN.
MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2020 June 24]. COL4A5 gene, [updated Dec 1; 2013.
cited 2022 August 16]
MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2020 June 24]. COL4A3 gene, [updated Dec 1; 2013.
cited 2022 August 16]
MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2020 June 24]. COL4A4 gene, [updated Dec 1; 2013.
cited 2022 August 16]
Jeffrey H. Miner Pathology vs. Molecular genetics: (re)defining the spectrum of Alport syndrome; 2014.
Pescucci C, Longo I, Bruttini M, Mari F, Renieri A. Type-IV collagen related diseases. J Nephrol. 2003 Mar-Apr; 16(2):314-6. Review. pixorize usmle 1 mnemonic Alport Syndrome | USMLE Step 1 Mnemonic - YouTube.
Ramesh Saxena, MD, PhD; Chief Editor: Vecihi Batuman, MD, FASN Jun 28, 2021 Alport syndrome - an Osmosis preview - YouTube.
Thorner PS. Alport syndrome and thin basement membrane nephropathy. Nephron Clin Pract. 2007;106(2):c82-8.
Epub 2007 June 6.
Brooke E. Howitt, Bradley J. Quade in diagnostic gynecologic and obstetric pathology (Third Edition), chapter 20- Uterine Mesenchymal Tumors; 2018.
Marc S. Levine, in Textbook of Gastrointestinal Radiology, 2-Volume set (Fourth Edition); 2022.
Omim Amme Complex, Alport Syndrome, Mental Retardation, Midface Hypoplasia, and Elliptocytosis; Creation: Victor A. McKusick, 6/1/1999. Contributors: Hilary J. Vernon-updated 04/28/2022.
Kashtan CE. Alport Syndrome. 2001 Aug 28 [Updated 2019 Feb 21]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022.
Kashtan CE, Ding J, Garosi G, Heidet L, Massella L, Nakanishi K, Nozu K, Renieri A, Rheault M, Wang F, Gross O. Alport syndrome: A unified classification of genetic disorders of collagen IV α345: a position paper of the Alport Syndrome Classification Working Group. KidneyInt. 2018;93:104551. [PubMed] [Reference list]
Chavez E, Rodriguez J, Drexler Y, Fornoni A. Novel therapies for alport syndrome. Front Med (Lausanne). 2022;9: 848389.
Published 2022 Apr 25. doi:10.3389/fmed.2022.848389
Duvall-Young J, Short CD, Raines MF, Gokal R, Lawler W. Fundus changes in mesangiocapillary glomerulonephritis type II: clinical and fluorescein angiographic findings. Br J Ophthalmol. 1989; 73(11):900-906.
Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F. Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. J Am Soc Nephrol. 2013;24(3):364–75.
DOI:10.1681/ASN.2012020148. PMID 23349312.
Hudson BG, Reeders ST, Tryggvason K. Type IV collagen: structure, gene organization, and role in human diseases. Molecular basis of Goodpasture and Alport syndromes and diffuse leiomyomatosis. J Biol Chem. 1993;268(35):26033–6. PMID 8253711.
Amari F, Segawa K, Ando F. Lens coloboma and Alport-like glomerulonephritis. Eur J Ophthalmol. 1994;(3):181–3. PMID 7819734
Lonsdale RN, Roberts PF, Vaughan R, Thiru S. Familial oesophageal leiomyomatosis and nephropathy. Histopathology. 1992;20(2):127–33. PMID 1559666
García-Torres R, Orozco L. Alport-leiomyomatosis syndrome: an update. Am J Kidney Dis. 1993;22(5):641–8. PMID 8238008.
McCarthy PA, Maino DM. Alport syndrome: A review. Clin Eye Vis Care. 2000;12(3–4):139–150.
Kaito H, Nozu K, Iijima K, Nakanishi K, Yoshiya K, Kanda K, Przybyslaw Krol R, Yoshikawa N, Matsuo M. The effect of aldosterone blockade in patients with Alport syndrome. Pediatr Nephrol 2006;21: 1824–1829. pmid:17039334
Gross O, Licht C, Anders HJ, Hoppe B, Beck B. Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int. 2012;81:494–501. pmid:22166847 [PubMed]
Gross O, Friede T, Hilgers R, Görlitz A, Gavénis K, Ahmed R, Dürr U. Safety and efficacy of the ACE-inhibitor ramipril in Alport syndrome: The double-blind, randomized, placebo-controlled, multicenter phase III EARLY PROTECT Alport trial in pediatric patients [published online July 1, 2012]. ISRN Pediatr.
DOI:10.5402/2012/436046pmid:22811928 [PubMed] Available:https://jasn.asnjournals.org/content/24/3/364
Koepke ML, Weber M, Schulze-Lohoff E, Beirowski B, Segerer S, Gross O. Nephroprotective effect of the HMG-CoA-reductase inhibitor cerivastatin in a mouse model of progressive renal fibrosis in Alport syndrome. Nephrol Dial Transplant. 2007;22:1062–1069. pmid:17287218 [PubMed]
Zeisberg M, Khurana M, Rao VH, Cosgrove D, Rougier JP, Werner MC, Shield CF, Werb Z, Kalluri R: Stage-specific action of matrix metalloproteinases influences progressive hereditary kidney disease. PLoS Med. 2006;3:e100. pmid:16509766
Ninichuk V, Gross O, Reichel C, Khandoga A. Delayed chemokine receptor 1 blockade prolongs survival in collagen 4A3-deficient mice with Alport disease. J Am Soc Nephrol. 2005;16:977–985. pmid:15716328 [PubMed]
Gross O, Koepke ML, Beirowski B, Schulze-Lohoff E, Segerer S, Weber M. Nephroprotection by antifibrotic and anti-inflammatory effects of the vasopeptidase inhibitor AVE7688. Kidney Int 2005;68:456–463. pmid:16014022 [PubMed]
Sugimoto H, Mundel TM, Sund M, Xie L, Cosgrove D, Kalluri R. Bone-marrow-derived stem cells repair basement membrane collagen defects and reverse genetic kidney disease. Proc Natl Acad Sci U S A. 2006;103:7321–7326. pmid:16648256
Prodromidi EI, Poulsom R, Jeffery R, Roufosse CA, Pollard PJ, Pusey CD, Cook HT. Bone marrow-derived cells contribute to podocyte regeneration and amelioration of renal disease in a mouse model of Alport syndrome. Stem Cells. 2006; 24:2448–2455.
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