Dent's disease

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at December 1, 2016
StartDent's disease

Dent’s disease, also known as Dent disease, is a rare genetic disorder affecting kidney function. There are two types of Dent’s disease, simply referred to as type 1 and type 2, caused by different gene defects. Symptoms are similar for patients with both types of the disease though type 2 tends to present with additional symptoms.

Contents

Definition & Facts

Dent’s disease is an X-linked recessive genetic disorder, meaning that the gene which causes the disease is carried on the X chromosome. Because males only have one X chromosome, Dent’s disease is far more common among men than among women, although women can be genetic carriers of the disease without showing symptoms.

Women who do exhibit symptoms generally experience milder symptoms than men and are less likely to suffer from end-stage renal failure. Since the gene responsible for Dent’s disease is only carried on the X chromosome, men cannot pass the disease on to their sons, but they will always pass the gene onto their daughters, making their daughters carriers of the disease.

Symptoms & Complaints

Symptoms of Dent’s disease usually appear in childhood for males, but because these symptoms can overlap with other disorders, it can be misdiagnosed.

The first sign of Dent’s disease is usually tubular proteinuria, which is proteinuria or the presence of an abnormally large amount of protein in the urine as a result of disease in the tubulointerstitial parts of the kidney (those structures of the kidney that are not the glomeruli).

Hypercalciuria (excess calcium in the urine) and kidney stones are other symptoms present in patients with this disease. Calcium deposits can also be present in the kidneys, and the presence of kidney stones can cause blood in the urine and moderate to severe abdominal pain.

Some patients can also develop a disorder in which the bones become soft and weak due to decreased levels of vitamin D and certain minerals. This condition is commonly known as rickets. People with the less common type 2 of Dent’s disease can also have other symptoms such as weak muscle tone and mild cataracts, although the cataracts generally do not impair vision to a noticeable extent.

Rarely, people with type 2 can exhibit mild intellectual disability in addition to the more common symptoms. Over time, kidney function will diminish until the patient enters end-stage renal failure, which is a life-threatening condition. 

Causes

Dent’s disease is not caused by any environmental factors or dietary factors and is not contagious. It is a genetic disorder, caused by a mutation of either the CLCN5 gene or the OCRL gene, both of which are found on the X chromosome. These genes are expressed in other areas throughout the body besides the kidneys, so it is still unclear why the kidneys are the organ that is most affected by the mutation.

A male who shows signs of the disease will never have inherited it from his father, although it is still possible for other paternal relatives to carry the disease. The mother is the carrier for all male patients with the disease, and it is possible that she may have other female relatives who carry the gene as well and likely has a male ancestor who exhibited signs of the disease. Females who have Dent's disease will have inherited the mutated gene from both their father and their mother, even if their mother showed no symptoms.

In a quarter of cases, the cause of Dent's disease is unknown.

Diagnosis & Tests

Diagnosis of Dent’s disease begins with a careful examination of symptoms. Proteinuria, hypercalciuria, and kidney stones can all be caused by other disorders, so it is important to rule out other causes before settling on a diagnosis of Dent’s disease.

Close examination of family history is crucial, although it is important to note that due to frequent misdiagnosis, a family history may not be conclusive. If ancestors or relatives have been diagnosed with other kidney disorders that show symptoms similar to those of Dent’s disease, it is possible that they carry the responsible gene even if they have been given a different diagnosis.

A genetic test should be ordered in order to confirm a diagnosis of Dent's disease. Testing should look at both the CLCN5 gene and the OCRL gene, although treatment is largely the same for both types of Dent’s disease.

Treatment & Therapy

There is currently no cure for Dent’s disease, and due to its extreme rarity, there have been few conclusive studies done on proper treatment protocols in managing the disease. As a result, there is no general consensus on effective and safe treatment methods.

Treatment generally centers on symptom management and palliative care to prevent kidney stones and support kidney function to delay the progression of kidney disease and to postpone the onset of end-stage renal failure.

Medications to prevent kidney stones are often used, although these can have the effect of dangerously lowering potassium and overall blood volume, so close monitoring is necessary when these medications are prescribed.

Patients who develop rickets as a complication of their disease can be treated with vitamin D supplements, but close monitoring is needed here as well in order to prevent increasing the occurrence of kidney stones due to increased calcium in the urine. Even with treatment, end-stage renal failure is likely to occur in early to middle adulthood. 

Prevention & Prophylaxis

The only prevention for Dent’s disease is genetic counseling. So far, only 250 families report being affected by the disease, making it exceedingly rare.

However, since a woman can be a carrier of the gene without showing symptoms, any woman who has a family history of Dent’s disease may opt to be tested in order to determine her risk for passing the mutated gene down to her children. Men who have Dent’s disease must be aware that they will pass the gene on to any female children.