Alport syndrome is a genetic disorder affecting around 1 in 5,00010,000 children, characterized by glomerulonephritis, endstage kidney disease, and hearing loss. Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Most male patients present with hematuria as children or young adults. Mar 18, 2017 alport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities. An algorithmic approach to renal biopsy interpretation of. In 85% of cases, it is caused by a mutation affecting the gene for type iv collagen, col4. Nov 20, 2012 the diagnosis of renal pathology associated wi th alport syndrome. A simple summary of glomerulonephritis pathology student. Kidney biopsy is unremarkable in early stages in males with x linked alport syndrome and in carriers, with afflicted patients. All patients with alport syndrome diffuse leiomyomatosis complex have been found to have deletions that span the 5 ends of the col4a5 and col4a6 genes. The alport syndrome foundation is a nonprofit organization dedicated to improving the lives of those affected by alport syndrome through education, empowerment, advocacy, and research.
Alport syndrome can also affect the eyes, though the changes do not usually affect sight, except when changes to the lens occur in later life. In most cases urine examination suggests presence of blood in urine also known as hematuria. Modification of an aggressive model of alport syndrome. Figure 3 alport syndrome with discontinuous staining for alpha 5 subtype of collagen type iv along glomerular basement membranes, bowmans capsule, and distal tubule basement membranes, consistent with a carrier state of xlinked alport syndrome in a female patient immunofluorescence microscopy. Tips on how to study smarter preparing for the mcat preparing to apply to med school clinicians corner. Female carriers of xlinked classic alport syndrome usually have only hematuria, but may develop progressive kidney disease as middleaged or older adults. Clinical presentation hematuria sensorineural hearing loss. An algorithmic approach to renal biopsy interpretation of glomerular diseases. Female carriers of xlinked classic alport syndrome usually have only hematuria, but may develop progressive. Affected women are commonly undiagnosed, but 15%30% develop renal. Alport syndrome also referred to as hereditary nephritis is an inherited progressive form of glomerular disease that is often associated with sensorineural hearing loss and ocular. Alport syndrome 35 diseases other than glomerulonephritis that typically cause acute renal failure 5% of biopsies, n371 thrombotic microangiopathy all types 126 acute tubulointerstitial nephritis 101 acute tubular necrosis 69 atheroembolization 34 light chain cast nephropathy 31 cortical necrosis 10. In this minimally invasive procedure, a doctor collects a small sample of kidney tissue with a needle. Genetic testing for alport syndrome in presymptomatic.
Additionally, lense abnormalities are not uncommon in this condition. Differential expression of basement membrane collagen chains in diabetic nephropathy. Pdf alport syndromeinsights from basic and clinical. Jci insight osteopontin deficiency ameliorates alport. Alport syndrome is a rare hereditary renal disorder with no etiologic therapy.
Nov 21, 2019 alport syndrome as is an inherited genetic disorder characterized by range of alterations from glomerular basement membrane abnormalities up to endstage renal disease. Progression of alport kidney disease in col4a3 knock out mice. Aug 29, 2018 alport syndrome or hereditary nephritis is a hereditary genetic disease. The spectrum of alport syndrome, from benign familial hematuria at one extreme to earlyonset endstage renal disease with hearing and eye defects at the other extreme. Kidney failure is not as common in females with alport syndrome.
The pathogenesis of alport syndrome involves type iv collagen molecules containing the. Dec 30, 2017 renal prognosis in alport syndrome depends on the kind of mutation causing the condition. It is caused by large or particularly severe mutations in the genes which code for collagen, a protein that helps build the part of the kidney filters glomeruli that is called the basement membrane. Iga nephropathy suspected to be combined with fabry. Goodpasture syndrome is a pulmonaryrenal syndrome, which is a group of acute illnesses involving the kidneys and lungs. Other manifestations of col4a3, col4a4, and col4a5 mutations, which can. Of 49 patients with kidney biopsy available for electron microscopy.
Renal disease in heptinstalls pathology of the kidney, 6th edition, jennette jc, olson jl, schwartz mm, silva fg eds, lww, 2007, chapter 3. Treatments targeting the gbm pathology of alport syndrome discoidin domain receptor 1 and integrin. It can also cause hearing loss and problems within the eyes. Feb 26, 2019 please use one of the following formats to cite this article in your essay, paper or report. Incidence of 1 per 5 10,000 in us ages 5 20 years, usually males or mosaic females causes 2. Sai ram keithireddy, raghu kalluri, in molecular and genetic basis of renal disease, 2008. The major constituent of the gbm is type iv collagen. Aug 24, 2019 alport syndrome as, a rare disease of basement membrane type iv collagen, impacts the kidneys, ears, and eyes.
On renal biopsy, podocyte hypertrophy was seen by light microscopy. Alport syndrome is a genetic disease of collagen iv. See the albuminuria and blood in urine fact sheets for more information. How to strike a balance in medical school clinicians corner. Proteinuria develops during teenage years, with nephrotic syndrome in. Progress in understanding the molecular mechanisms of glomerular pathology. Alport syndrome as is a hereditary disease of the glomerular basement membrane in the kidney characterized by progressive renal failure, sensorineural deafness, andor ocular abnormalities. Outcomes of kidney transplantation in alport syndrome compared with other forms of renal disease. The clinical manifestations of syndrome are characterized by glomerulonephritis, end stage renal disease, abnormal vision and acute hearing loss. Mark haas 2009 alport syndrome and thin glomerular basement membrane nephropathy.
Alport syndrome genetic and rare diseases information. Alpers, md2 clinical and pathologic features patients with alport syndrome present with he. Become an osmosis prime member today and access over 1,200 videos with comprehensive. Alport syndrome is an xlinked dominant disease characterized by progressive sensorineural hearing loss, renal disease and, at times, ocular lesions.
Consequently, proper differential diagnosis for as should rule out all other causes of hematuria. Other manifestations of col4a3, col4a4, and col4a5 mutations, which can vary even within a family, fall between the extremes in what are likely overlapping positions. Kidney failure alport syndrome always causes kidney failure in males, which usually happens between the ages of 15 and 50 years. The discovery that alport syndrome was caused by mutations in type iv collagen genes lead to early speculation regarding how. We were initially able to identify 1601 articles using electronic and manual research. Alport syndrome and thin glomerular basement membrane. Most cases of alport syndrome are xlinked and caused by a mutation in a gene encoding type iv collagen. It is caused by large or particularly severe mutations in the genes which code for collagen, a protein that helps build the part of the kidney filters. Alport syndrome is a disease of the filter part of the kidneys. A key alport syndrome diagnostic tool is a kidney biopsy. Alport syndrome 35 diseases other than glomerulonephritis that typically cause acute renal failure 5% of biopsies, n371 thrombotic microangiopathy all types 126 acute tubulointerstitial nephritis. Planned and ongoing clinical studies using targets and therapeutic approaches discussed herein provide new hope for as patients. Renal failure, 226, 751758 2000 proceedings renal pathology and ultrastructural findings in alports syndrome laurehe.
Alport syndrome is a rare genetic disease that results in disordered basement membrane type iv collagen resulting in occular and auditory defects as well of progressive kidney disease. Mutations in the col4a5 xlinked, or col4a3 and col4a4 autosomal recessive genes result in absence of the collagen iv. Alport syndrome is a primary basement membrane disorder arising from mutations in genes encoding several members of the type iv collagen protein family. People with alport syndrome experience progressive loss of kidney function. How to tackle your first semester of med school surviving and thriving in first year clinicians corner. Male patients with xlinked alport progress to endstage kidney disease, usually in adulthood. Dialysis and kidney transplantation in alport syndrome 9 outcomes of male patients with alport syndrome undergoing renal replacement therapy. Almost all affected individuals have blood in their urine hematuria, which indicates abnormal functioning of the kidneys.
Alport syndrome, col4a5, gene variant, mutation database, phenotype introduction alport syndrome as is a progressive inherited renal disease characterized by persistent hematuria. Alport syndrome and thin glomerular basement mem brane nephropathy. Alport syndrome develops when the body cannot produce enough type iv collagen, a protein vital to maintaining kidneys filtering capabilities how alport syndrome affects kidneys. Glomeruli are the tiny filtering units inside your kidneys. If alport syndrome is suspected, a doctor will perform a kidney biopsy to look for signs of the disease in the kidneys, especially abnormalities in their filtering membranes.
The glomerular basement membrane gbm is a sheetlike structure between the capillary endothelial cells and the visceral epithelial cells of the renal glomerulus. Samuelson i 1department of genetics, boys town national research hospital, omaha, nebraska 681 usa. Male patients with xlinked alport progress to endstage kidney disease. The pathogenesis of alport syndrome involves type iv collagen molecules containing the alpha 3iv chain. The probability of esrd in people younger than 30 years is significantly higher 90% in patients with a large rearrangement of the col4a5 gene than it is in those with minor mutations 5070%. Heres the complete overview of diagnostic atlas of renal pathology 2nd edition pdf. The renal lesions of alport syndrome american society of. Alport syndrome in women and girls american society of.
Alport syndrome is a hereditary cause of nephritis, but also of highfrequency nerve deafness. Most affected individuals experience progressive loss of kidney function, usually resulting in endstage kidney disease. Alport syndrome is a hereditary glomerulonephritis accompanied usually by sensorineural deafness, frequently by ocular abnormalities, and rarely by diffuse leiomyomatosis dl, which is characterized by benign nodular smooth muscle tumors of esophagus, tracheobronchial tree. We found that osteopontin opn is highly expressed in the renal tubules of the alport mouse and plays a causative pathological. Evidence from antigbm nephritis after renal transplantation. Alport syndrome is a disease that damages the tiny blood vessels in your kidneys. Fogo, md and michael kashgarian, md, delivers practical, highly visual.
Pdf alport syndromeinsights from basic and clinical research. This study was designed to investigate sexphenotype correlations and evaluate the contribution of macrophage infiltration to disease progression using col4a3 knock out col4a3ko mice, an established genetic model of autosomal recessive alport syndrome. Dec 30, 2017 kelly yp, patil a, wallis l, murray s, kant s, kaballo ma, et al. Truly congenital hearing loss is unlikely to be due to alport syndrome p. Alport syndrome can have different inheritance patterns. Inheritance is xlinked 85% or autosomal recessive 15%. Renal disease with hearing loss, even if familial, should not be equated with alport syndrome.
Treatment of these mice, before the onset of proteinuria, with broadly active inhibitors of mmps ameliorated alport renal disease progression. Carriers of rare autosomal recessive variants of alport syndrome also have hematuria. Alport syndrome is an inhertied disease with diverse clinical presentations, arising from mutations in genes encoding polypeptide chains of type iv collagen. Goodpasture syndrome includes all of the following conditions. Kidney biopsy is unremarkable in early stages in males with xlinked alport syndrome and in carriers, with afflicted patients. Sglt2 inhibitors a potential treatment for alport syndrome. Alport s syndrome as is caused by defects in the genes encoding type iv collagen of the basement membrane. Alpers, md2 clinical and pathologic features patients with alport. Alport syndrome is an inhertied disease with diverse clinical presentations, arising from mutations in genes. Many renal physicians think of alport syndrome as primarily affecting men. In severe cases, kidney failure occurs during adolescence or early adulthood, so most research has focused on remedies for kidney dysfunction. Because of the possibility of alport syndrome, a skin biopsy was performed in the boy. Diagnostic atlas of renal pathology 2nd edition pdf free.
Treatments targeting the gbm pathology of alport syndrome. Alport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities. Alport syndrome differential diagnoses medscape reference. Fogo, md and michael kashgarian, md, delivers practical, highly visual guidance for effectively and accurately diagnosing a wide range of pathologic entities. Dec 31, 2019 ccl2mcp1 blockade reduces glomerular and interstitial macrophages but does not ameliorate renal pathology in collagen4a3deficient mice with autosomal recessive alport nephropathy. Features of diagnostic atlas of renal pathology 2nd edition pdf heres a quick overview of the important features of this book. Pdf clinical trial recommendations for potential alport.
Alport syndrome with bilateral simultaneous anterior and. The pathogenesis, genetics, and pathology of alport syndrome are discussed separately. Pdf alports syndrome as is a progressive glomerulonephritis which is. Alport syndrome causes damage to your kidneys by attacking the glomeruli. This gene is located on the x chromosome, which is one of the two sex chromosomes. The discovery that alport syndrome was caused by mutations in type iv collagen genes lead to early speculation regarding how the alteration in basement membrane collagen composition caused the classic gbm ultrastructural dysmorphologies and podocyte foot process effacement associated with glomerular disease progression. In males who have only one x chromosome, one altered copy of the col4a5 gene in each cell is sufficient to cause kidney failure and other severe. Alport syndrome fact sheet kidney health australia. Download diagnostic atlas of renal pathology 2nd edition. See more than 700 high quality representative images of light, immunofluorescence, and electron microscopy for each diagnostic entity with correlations to clinical presentation and pathogenesis.