Alport syndrome is a genetic condition characterized by the progressive loss of kidney function and hearing. Alport syndrome can also affect the eyes. The presence of blood in the urine (hematuria) is almost always found in this condition. The International Statistical Classification of Diseases and Related Health Problems (commonly known by the abbreviation ICD) is a detailed description of known diseases and injuries. ... The following codes are used with International Statistical Classification of Diseases and Related Health Problems. ... // Q00-Q99 - Congenital malformations, deformations and chromosomal abnormalities (Q00-Q07) Congenital malformations of the nervous system (Q00) Anencephaly and similar malformations (Q01) Encephalocele (Q02) Microcephaly (Q03) Congenital hydrocephalus (Q04) Other congenital malformations of brain (Q05) Spina bifida (Q06) Other congenital malformations of spinal cord (Q07) Other congenital malformations of nervous... The International Statistical Classification of Diseases and Related Health Problems (commonly known by the abbreviation ICD) is a detailed description of known diseases and injuries. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Diseases Database is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... MedlinePlus (medlineplus. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... A genetic disorder, or genetic disease, is a condition caused by abnormal expression of one or more genes resulting in a clinical phenotype. ... The kidneys are bean-shaped excretory organs in vertebrates. ... Human blood smear: a - erythrocytes; b - neutrophil; c - eosinophil; d - lymphocyte. ... This article or section is in need of attention from an expert on the subject. ... In medicine, hematuria (or haematuria) is the presence of blood in the urine. ...

It was first identified in a British family by Dr. Cecil A. Alport in 1927. Dr. Cecil A. Alport (1880-1959) was an English internist who first identified the Alport syndrome in a British family in 1927. ...

Causes

Alport syndrome is caused by mutations in COL4A3, COL4A4, and COL4A5, collagen biosynthesis genes. Mutations in any of these genes prevent the proper production or assembly of the type IV collagen network, which is an important structural component of basement membranes in the kidney, inner ear, and eye. Basement membranes are thin, sheet-like structures that separate and support cells in many tissues. When mutations prevent the formation of type IV collagen fibers, the basement membranes of the kidneys are not able to filter waste products from the blood and create urine normally, allowing blood and protein into the urine. The abnormalities of type IV collagen in kidney basement membranes cause gradual scarring of the kidneys, eventually leading to kidney failure in many people with the disease. In biology, mutations are changes to the genetic material (either DNA or RNA). ... Tropocollagen triple helix. ... The kidneys are bean-shaped excretory organs in vertebrates. ... Bat ears come in different sizes and shapes The ear is the sense organ that detects sound. ... The human eye. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ...

Inheritance patterns

Alport syndrome can have different inheritance patterns that are dependent on the genetic mutation.

• In most people with Alport syndrome, the condition is inherited in an X-linked pattern, due to mutations in the COL4A5 gene. A condition is considered X-linked if the gene involved in the disorder is located on the X chromosome. In males, who have only one X chromosome, one altered copy of the COL4A5 gene is sufficient to cause severe Alport syndrome, explaining why most affected males eventually develop kidney failure. In females, who have two X chromosomes, a mutation in one copy of the COL4A5 gene usually results in blood in the urine, but most affected females do not develop kidney failure. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked diseases to their sons.

• Alport syndrome can be inherited in an autosomal recessive pattern if both copies of the COL4A3 or COL4A4 gene, located on chromosome 2, have been mutated. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.

Sex-linked genes are those carried on the mammalian X chromosome but not the Y chromosome. ... The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals (the other is the Y chromosome). ... In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ... Chromosome 2 is one of the 23 pairs of chromosomes in humans. ...

Criteria for the clinical diagnosis

Gregory et al, 1996, give the following 10 criteria for the diagnosis of Alport syndrome, 4 of the 10 criteria must be met:

• Family history of nephritis of unexplained haematuria in a first degree relative of the index case or in a male relative linked through any numbers of females.
• Persistent haematuria without evidence of another possibly inherited nephropathy such as thin GBM disease, polycystic kidney disease or IgA nephropathy.
• Bilateral sensorineural hearing loss in the 2000 to 8000 Hz range. The hearing loss develops gradually, is not present in early infancy and commonly presents before the age of 30 years.
• A mutation in COL4An (where n = 3, 4 or 5).
• Immunohistochemical evidence of complete or partial lack of the Alport epitope in glomerular, or epidermal basement membranes, or both.
• Widespread GBM ultrastructural abnormalities, in particular thickening, thinning and splitting.
• Ocular lesions including anterior lenticonus, posterior subcapsular cataract, posterior polymorphous dystrophy and retinal flecks.
• Gradual progression to ESRD in the index case of at least two family members.
• Macrothrombocytopenia or granulocytic inclusions.
• Diffuse leiomyomatosis of esophagus or female genitalia, or both.

Nephritis is inflammation of the kidney. ... The index case or patient zero is the initial patient in the population sample of an epidemiological investigation. ... Thin basement membrane disease (also known as benign familial hematuria and thin basement membrane nephropathy) is, along with IgA nephropathy, the most common cause of asymptomatic hematuria. ... Polycystic kidney disease (PKD) is a progressive, genetic disorder of the kidneys. ... IgA nephropathy (also known as IgA nephritis, IgAN, Bergers disease and synpharyngitic glomerulonephritis) is a form of glomerulonephritis (inflammation of the glomeruli of the kidney). ... Sensorineural hearing loss is a type of hearing loss in which the root cause lies in the vestibulocochlear nerve (Cranial nerve VIII), the inner ear, or central processing centers of the brain. ... In biology, mutations are changes to the genetic material (either DNA or RNA). ... Immunohistochemistry or IHC refers to the process of localizing proteins in cells of a tissue section exploiting the principle of antibodies binding specifically to antigens in biological tissues. ... An epitope is the part of a macromolecule that is recognized by the immune system, specifically by antibodies, B cells, or cytotoxic T cells. ... The Game Boy Micro Game Boy Micro (GBM) is a micro sized Game Boy Advance set for release by Nintendo in the fall of 2005. ... Chronic renal failure (CRF, or chronic kidney failure, CKF) is a slowly progressive loss of renal function over a period of months or years and defined as an abnormally low glomerular filtration rate, which is usually determined indirectly by the creatinine level in blood serum. ... A leiomyoma (plural is leiomyomata) is a benign smooth muscle neoplasm that is not premalignant. ... The esophagus (also spelled oesophagus/Å“sophagus), or gullet is an organ in vertebrates which consists of a muscular tube through which food passes from the mouth area to the stomach. ... The human females reproductive system. ...

References

• Kashtan CE. Michael AF. Alport syndrome. Kidney International. 50(5):1445-63, 1996 Nov.[1]
• Tryggvason K. Heikkila P. Pettersson E. Tibell A. Thorner P. Can Alport syndrome be treated by gene therapy?. Kidney International. 51(5):1493-9, 1997 May.
• Gregory MC et al: Alport syndrome clinical phenotypes, incidence and pathology, in Molecular Pathology and Genetics of Alport Syndrome (vol 117), edited by Tryggvason K, Basel, Karger, 1996, pp 1-28

This article incorporates public domain text from The U.S. National Library of Medicine

External links

• Alport syndrome - Geneva Foundation for Medical Education and Research