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What is Dent Disease?

Dent Disease is a rare genetic disorder that affects the kidneys. Typical problems are leakage of proteins into the urine and large amounts of calcium in the urine. Kidney stones are common. People with Dent Disease can develop kidney damage, even kidney failure. Kidney dialysis or transplantation may be necessary. The disease is maybe diagnosed in childhood, but can be silent for years.

Who gets Dent Disease?

Males are more often affected by Dent disease than women, but women can also have a mild case of the disease. Dent affects people all over the world. Currently we do not know how many people have Dent.

What causes Dent Disease?

The most common Dent disease is a defect in two genes. There are two main types of Dent, type 1 and type2. Type 1 is more common, which is caused by a defect in a protein gene can cause proteinuria (increased amounts of protein in urine). Type 2 is an enzyme abnormality in kidney cell function called that causes hypercalciuria (large amounts of calcium in the urine).

How is Dent Disease diagnosed?

Patients that have kidney stone with proteinuria and hypercalciuria can have a genetic test to confirm which gene is not functioning correctly.

What is/is there treatment for Dent Disease?

There is currently no cure for Dent disease, but there are treatments we can offer. Some medications (diuretics) can be given to lower the calcium in the urine and hopefully reduce the risk of kidney stones. Studies have shown that a high citrate diet may delay the loss of kidney function, so potassium citrate can be given to patients with Dent Disease. However, studies in patients are badly needed to determine if either of these treatments is effective in Dent Disease.

Frequently Asked Questions About Dent Disease

How is Dent Disease diagnosed?

A physician may suspect Dent disease by observing a number of clinical markers including (but not limited to): protein in the urine, excessive amino acid excretion, excessive urinary calcium excretion, reduced levels of parathyroid hormone, increased levels of vitamin D or the presence of kidney stones made of calcium oxalate or calcium phosphate. A definitive diagnosis can be made by genetic testing of the patient. If the patient’s genetic material includes Dent Disease-specific mutations, the diagnosis is confirmed.

Do only males get Dent Disease?

Men have a more severe form of the disease while women may only have mild symptoms if any at all. Since Dent Disease is X-linked, females can be carriers (i.e. have one normal and one affected X chromosome). Although carrier females do not appear to have any serious health consequences, they do often have urinary findings that are not quite normal. 

Can females get Dent disease?

Since it is an X-linked disorder, women or girls can be carriers but usually only have very mild manifestations that can be detected on laboratory tests, but do not cause kidney stones or loss of kidney function.

What age do patients present?

Many patients are diagnosed as children because of kidney stones, bone disease or abnormally high levels of protein in the urine. However, some persons can remain undiagnosed well into adulthood.

What is the most common symptom for Dent Disease?

The most common symptoms that patients with Dent's disease experience are related to the passage of kidney stones, such as pain or blood in the urine.

What is the best screening test for Dent disease?

Testing the urine for smaller proteins (so called low molecular weight proteins) is a very good screening test, since the urine levels of these proteins are usually quite high in affected patients. Good proteins to test for are retinol binding protein and alpha 1 microglobulin.

How can a definite diagnosis of Dent disease be made?

A typical clinical presentation with low molecular weight proteinuria and hypercalciuria is very suggestive of Dent disease. The diagnosis can be confimrmed by genetic testing of two genes knwn to cause Dent disease (CLCN5 and ORCL1). There are still some patients who have features of Dent disease but lack mutations in these two genes.

Once a person is diagnosed with Dent disease, should other members of the family be screened?

If a male is diagnosed with Dent disease, each of his brothers has a 50% chance of being affected. Screening the urine of these siblings for low molecular weight proteins should detect most of the affected siblings. This might identify persons who would benefit from careful follow-up to treat potential Dent disease manifestations (bone disease, kidney stones, chronic kidney disease). However, whether or not to screen siblings of an affected patient is a decision best made in consultation with your doctor.

What is the best treatment for Dent disease?

There is currently no known cure for Dent disease. However, there are treatments that have been used for certain manifestations of the disease. Oral phosphorous may be necessary for certain patient with bone disease. The diuretic hydrochlorothiazide (or other diuretics in this class) has been used to reduce urinary calcium levels in Dent patients. This should reduce the rate of stone formation, and potentially help to preserve kidney function. Oral potassium citrate has also been used to reduce the rate of stone formation in Dent patients, and was effective in an animal model of the disease. However, since Dent disease is rare, there have not been enough patients to enroll in clinical trials to prove the effectiveness of any one given approach.

Treatment includes keeping the kidneys as healthy as possible and efforts are targeted to reducing kidney scarring and preventing kidney failure associated with Dent Disease. Treatments may include medications, diet modifications and possibly kidney transplantation.

How is Dent disease connected to Lowe syndrome?

Some patients with typical Dent disease findings (high levels of calcium and low molecular weight proteins in the urine) were found to have a mutation the same gene that causes Lowe Syndrome (OCRL1). However, many patients with mutation in the OCRL1 gene do not have these urinary findings, and patients with Lowe Syndrome have not been found with CLCN5 mutations (the gene that has mutations in most patients with Dent disease).

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