Benign familial hematuria, also known as thin-basement-membrane nephropathy, is a kidney disease that usually begins during childhood. The disorder is characterized by the presence of red blood cells in the urine (hematuria). The blood in the urine may be present in microscopic amounts (microscopic hematuria) and not visible to the eye, present in small amounts that give the urine a "cloudy" or "smoky" appearance, or easily visible. Many individuals with the disorder have abnormalities of the kidney's glomeruli, the clusters of small blood vessels (capillaries) that normally filter the blood passing through the kidneys (glomeruli filtration). In such cases, the membrane (basement membrane) supporting the loops of capillaries that make up the renal glomeruli may be abnormally thin. Benign familial hematuria may be inherited as an autosomal dominant genetic trait.
Benign familial hematuria is a nonprogressive kidney disorder that usually begins in childhood and is characterized by the presence of red blood cells in the urine (hematuria) and scattered thinning of microscopic parts of the kidney (glomerular basement membranes). The amount of blood in the urine may be microscopic or visible, and is often preceded by a respiratory infection. Unlike other kidney disorders, there is little or no blood plasma protein in the urine (proteinuria), and there is no change in the renal (kidney) function. In children with this disorder, there may be a clearing of the urine after each episode; in adults, the blood in the urine may be more persistent.
Benign familial hematuria is most often inherited as an autosomal dominant genetic trait. The disorder is thought to occur as a result of changes (mutations) in genes involved in the production of a substance known as collagen complex 4 that helps form the basement membrane. Genes COL4A3 and COL4A4 on the long arm of chromosome 2 (2q35-q37) are thought to be involved.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 2q35-q37” refers to a region on the long arm of chromosome 2 between the 35th and 37th bands. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.
X-linked dominant disorders are also caused by an abnormal gene on the X chromosome, but in these rare conditions, females with an abnormal gene are affected with the disease. Males with an abnormal gene are more severely affected than females, and many of these males do not survive.
Benign familial hematuria occurs more frequently in males than females, and more often in children and young adults.
Most cases of benign familial hematuria are found by accident. While a search is being conducted for other suspected problems, the characteristic microscopic blood in the urine (hematuria) is detected. The diagnosis may be confirmed by a thorough clinical evaluation that includes a detailed patient history and laboratory tests that confirm the presence of blood in the urine. In addition, tissue samples from the kidneys of affected individuals may be obtained during a biopsy procedure and then examined under an electron microscope. These studies may reveal structural abnormalities within the kidneys (i.e., abnormally thin glomerular basement membrane).
Since benign familial hematuria is usually not a progressive disease, treatment may not be necessary. However, since a small percentage of cases may progress to chronic kidney disease, routine examination and urine tests may be necessary to monitor for changes in kidney function. Genetic counseling will be of benefit for people with this disease and their families. Other treatment is symptomatic and supportive.
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