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What Is Dent's Disease?
Dent's disease (DD), which is also sometimes referred to as Dent disease, is a genetic disorder that causes a host of kidney problems in those who suffer from it. Such problems include, but are not limited to:
- Increased incidence of kidney stone formation
- Increased protein in urine (which causes urine to be foamy)
- Loss of calcium from the body (via urine)
- Progressive kidney failure (which occurs in 30 to 80 percent of affected males between age 20 and age 50)
- Night blindness
- In some cases, rickets develops (rickets is a condition in which significant bone softening occurs)
- In the worst cases, DD can be fatal
Fortunately, DD is a very rare condition, as it has been estimated that it affects only about 250 families worldwide. Even though it is an X-linked genetic disorder (as described in more detail below), about half of all known DD sufferers are female. However, DD affects males more severely than it does females.
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Molecular biologists have determined that mutations in two genes, which are designated CLCN5 and ORCL1, are genetic causes of DD. Both of these genes are located on the X chromosome.
In normal individuals, the CLCN5 gene encodes a calcium channel protein that functions within the cell membrane to shuttle calcium ions in and out of cells, and the ORCL1 gene encodes a protein that is involved in cell signaling. Those who have a mutation in either one of these genes cannot carry out proper calcium ion export or cell signaling. In either case, certain kidney cells function improperly and the defects and complications described above result.
Interestingly, about 20 percent of individuals who have DD do not have a mutation in either the CLCN5 gene or the ORCL1 gene. It is anticipated that these individuals have a mutation in some other gene or genes that has/have yet to be identified. Molecular geneticists are currently working to identify this gene or genes.
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Diagnosis And Treatment Issues
DD is a tricky condition to diagnose initially. In a typical diagnosis scheme, a patient will be diagnosed as having DD if the following three criteria are met:
(1) the patient has a high protein level in his/her urine;
(2) the patient has excess calcium in his/her urine; and
(3) the patient is prone to developing kidney stones or has other significant kidney problems.
Once this preliminary diagnostic step is carried out, absolute confirmation can come from the later identification of a mutation (or mutations) in either one of the CLCN5 and ORCL1 genes. However, as mentioned above, some DD-affected individuals do not have a mutation in either of these genes, so failure to detect a mutation should not be used alone as evidence to rule out DD in making the diagnosis.
Finally, there is no substantially effective method or drug for treating DD and there is no cure for this condition. Scientists are making efforts, however, to develop gene therapy methods that they believe will cure, or at least alleviate, the symptoms suffered by DD patients.
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H.K. Burgess et al., Dent's disease: Can we slow its progression?, Nephrology Dialysis Transplantation, 2001.
Mayo Clinic, Dent's Disease: http://mayoresearch.mayo.edu/mayo/research/nephrology/renal_stone_disease.cfm
M. Bald, U. Vester, and A.-M. Wingren, Dent's Disease, Nephrology Dialysis Transplantation, 2002: http://ndt.oxfordjournals.org/content/17/3/520.full.pdf+html
O. Devuyst and R. V. Thakker, Debt's Disease, Orphanet Journal of Rare Diseases: http://www.ojrd.com/content/5/1/28
R.R. Hoopes et al., Dent's Disease with Mutations in OCRL1, American Journal of Human Genetics,2005: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1196371/