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Renal glycosuria, also known as renal glucosuria, is a rare condition in which the simple sugar glucose is eliminated (excreted) in the urine despite normal or low blood glucose levels. With normal kidney (renal) function, glucose is excreted in the urine only when there are abnormally elevated levels of glucose in the blood. However, in those with renal glycosuria, glucose is abnormally eliminated in the urine due to improper functioning of the renal tubules, which are primary components of the filtering units of the kidneys (nephrons). In most affected individuals, the condition causes no apparent symptoms (asymptomatic) or serious effects. When renal glycosuria occurs as an isolated finding with otherwise normal kidney function, the condition is thought to be inherited as an autosomal recessive trait.
In individuals with renal glycosuria, glucose is excreted in the urine in the presence of normal or low concentrations of blood glucose. With normal renal function, as blood flows through the kidneys, glucose and other substances are filtered from the fluid portion of the blood. The filtrate of the blood then moves through a network of canals known as renal tubules, where most of the filtered substances, including glucose, sodium, and water, are reabsorbed and returned to the bloodstream, while certain unwanted substances are eliminated in the urine. In those with proper renal functioning, glucose is excreted into the urine only when there are abnormally elevated levels of the sugar in the blood. However, in individuals with renal glycosuria, there is a lowered renal threshold to glucose and, in some cases, a reduction in the rate at which the renal tubules are able to reabsorb glucose. (For more, see "Causes" below.)
In most affected individuals, renal glycosuria is a benign condition, resulting in no apparent symptoms (asymptomatic). However, in some cases, glycosuria may be pronounced enough to result in excessive urination (polyuria), excessive thirst (polydipsia), and other associated symptoms. Less commonly, under certain conditions, such as pregnancy or starvation, renal glycosuria may be associated with excessively low levels of bodily fluids (dehydration) or a condition in which there is an abnormal accumulation of certain chemical substances (ketone bodies) in bodily tissues and fluids due to excessive breakdown of fats (ketosis).
Renal glycosuria is considered an inherited defect of membrane transport (i.e., an abnormal renal transport syndrome). Membrane transport disorders are characterized by abnormalities in the movement (i.e., transport) of one or more compounds across cell membranes. They are thought to result from genetic changes (mutations) causing alterations in specific membrane proteins.
As noted above, due to impaired renal tubular functioning, renal glycosuria is characterized by a reduction in the blood glucose concentration at which glucose begins to be excreted in urine (reduced renal threshold for glucose) and, in some instances, a reduction in the maximum rate at which glucose may be reabsorbed into the bloodstream (reduced transport maximum [tubular maximum for glucose or "TmG"]). Researchers have classified renal glycosuria into two major subtypes based upon the presence of such defects: type A (low threshold, reduced TmG) and type B (low threshold, normal TmG). In addition, investigators have described a form of renal glycosuria termed type 0, in which there is complete absence of renal tubular glucose reabsorption.
Isolated renal glycosuria with otherwise normal kidney function is thought to be transmitted as an "incompletely" recessive trait (see below). Human traits, including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother.
In autosomal recessive disorders, the condition may not appear unless a person inherits a defective (mutated) 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 of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease but generally will not show symptoms. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.
Early studies suggested that renal glycosuria was transmitted as an autosomal dominant trait, meaning that inheriting just one copy of the disease gene from either the mother or father could result in full expression of the condition. However, more recent research suggests that the trait is incompletely recessive. In other words, individuals who inherit one mutated copy of a gene for renal glycosuria (heterozygous carriers) may have modest glycosuria due to mild reductions in the renal threshold for glucose or the maximum rate at which glucose is reabsorbed. Yet heavy, consistent renal glycosuria is associated with inheritance of two copies of the same gene mutation (homozygosity) for the condition; in addition, it is possible that individuals with renal glycosuria may inherit one copy of two different gene mutations (compound heterozygotes). Investigators have observed that renal glycosuria types A and B have occurred in members of the same family. In such cases, both parents may be normal or may have abnormal renal tubular transport of glucose. Based on such evidence, experts suggest that several different gene mutations affecting one or more renal glucose transport systems may be involved in causing renal glycosuria.
In some affected families (kindreds), renal glycosuria appears to result from mutations of a gene (currently designated "GLYS1") that has been mapped to the short arm (p) of chromosome 6 (6p21.3). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as "p" and a long arm identified by the letter "q." Chromosomes are further subdivided into bands that are numbered. Therefore, 6p21.3 refers to band 21.3 on the short arm of chromosome 6.
According to researchers, in such families, the gene for renal glycosuria appears to be closely linked with another, previously identified gene (known as the "HLA" gene) located at this chromosomal region.
Some investigators have also suggested that renal glycosuria may be caused by changes in a gene known as "SLC5A2" (also called the renal sodium-glucose cotransporter gene). However, this gene has been mapped to chromosome 16 (16p11.2).
Further research is needed to learn more about the underlying genetic mechanisms responsible for the transmission and expression of this condition.
Renal glycosuria is a rare condition that appears to affect males and females in equal numbers. Reported cases of the disorder include affected individuals in several multigenerational families (kindreds). In most individuals with renal glycosuria, no associated symptoms are apparent (asymptomatic). Less commonly, under certain conditions, such as during pregnancy or starvation, serious symptoms and findings may become apparent (e.g., dehydration, ketosis).
Certain features of the following disorders may be similar to those associated with renal glycosuria. Comparisons may be useful for a differential diagnosis:
Diabetes mellitus is a common disorder characterized by abnormally high blood sugar (glucose) levels due to deficiency or resistance to the effects of insulin. The hormone insulin promotes the movement of glucose into cells for the body's energy needs or liver and fat cells for storage purposes. Insufficient insulin may lead to inadequate absorption of glucose; increased glucose levels in the blood (hyperglycemia) and urine (glycosuria); impaired fat metabolism; and increased degeneration of certain blood vessels. Associated symptoms and findings may include excessive urination (polyuria) and increased thirst (polydipsia), excessive hunger and eating (polyphagia), and the development of particular complications without appropriate treatment. Although the exact causes of diabetes mellitus are not known, genetic factors are thought to play some role. (For more information on this disorder, choose "diabetes" as your search term in the Rare Disease Database.)
Fanconi's syndrome is a general term referring to a renal condition that may occur as an isolated finding; in association with certain genetic disorders, particularly the metabolic disorder cystinosis; or as an acquired condition, such as due to drug toxicity, kidney transplantation, vitamin D deficiency, or exposure to certain heavy metals. Fanconi's syndrome is characterized by generalized, abnormal functioning of the first portion of the renal tubules (proximal renal tubules). Associated symptoms and findings may include high acidity of the blood and abnormally increased levels of glucose, phosphates, bicarbonate, and particular amino acids in the urine. (For further information, choose "Fanconi*" and "cystinosis" as your search terms in the Rare Disease Database.)
Hypophosphatemic rickets refers to a group of disorders of proximal renal tubular dysfunction characterized by loss of phosphate, insufficient levels of the active form of vitamin D, decreased intestinal absorption of calcium, and associated skeletal deformities. Symptoms and findings may include excessive excretion of phosphate in the urine, low blood phosphate levels, bone softening (osteomalacia) and pain, bowing of the legs, short stature, and/or other features. The condition may be inherited or develop due to certain cancers.
Renal glycosuria is diagnosed based upon laboratory tests that confirm the presence of glucose in the urine in association with normal or low blood glucose levels. (Such testing is typically conducted after overnight fasting.)
In most affected individuals, no treatment is required. However, some individuals with renal glycosuria may develop diabetes mellitus. (For further information, please see the "Related Disorders" section above.) Therefore, appropriate testing should be conducted to rule out diabetes and to regularly monitor those with confirmed renal glycosuria.
Genetic counseling will be of benefit for affected individuals and their families. Other treatment for this condition is symptomatic and supportive.
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FROM THE INTERNET
Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 233100; 2/5/01. Available at: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?233100.
Report last updated: 2007/09/17 00:00:00 GMT+0