Renal Glycosuria

Renal Glycosuria

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Renal Glycosuria is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Renal Glucosuria
  • Benign Glycosuria
  • Familial Renal Glycosuria
  • Nondiabetic Glycosuria
  • Primary Renal Glycosuria

Disorder Subdivisions

  • Renal Glycosuria, Type A
  • Renal Glycosuria, Type B
  • Renal Glycosuria, Type O

General Discussion

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.

Symptoms

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).

Causes

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.

Affected Populations

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).

Standard Therapies

Diagnosis

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.)



Treatment

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.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Beers MH, et al., eds. The Merck Manual. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:1901.



Fauci AS, et al., eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill Companies, Inc; 1998:2204, 2207.



Buyse ML. Birth Defects Encyclopedia. Dover, Mass: Blackwell Scientific Publications, Inc; 1990:1463-64.



Stanbury JB, et al., eds. The Metabolic Basis of Inherited Disease. 5th ed. New York, NY: McGraw-Hill Companies Inc; 1983:1806.



JOURNAL ARTICLES

Bamba T, et al. Familial renal glycosuria. Ryoikibetsu Shokogun Shirizu. 1998;19:555-56.



Kanai Y, et al. The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. J Clin Invest. 1994;93:397-404.



Oemar BS, et al. Complete absence of tubular glucose reabsorption; a new type of renal glucosuria. Clin Nephrol. 1987;27:156-60.



De Marchi S, et al. Close genetic linkage between HLA and renal glycosuria. Am J Nephrol. 1984;4:280-86.



De Marchi S, et al. Renal glycosuria: dominant or recessive autosome anomaly? Mode of hereditary transmission based on the analysis of a 3-generation family tree. Minerva Med. 1983;74:301-06.



Elsas LJ, et al. Autosomal recessive inheritance of renal glycosuria. Metabolism. 1971;20:968-75.



Elsas LJ, et al. Familial renal glycosuria: a genetic reappraisal of hexose transport by kidney and intestine. J Clin Invest. 1969;48:1845-54.



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.

Resources

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For a Complete Report

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