Dent Dsease is a rare kidney condition that affects males (see ‘How the disease works’ below). The disease is very variable. Some patients are only mildly affected. Symptoms often develop gradually in childhood or early adulthood. In some patients it is discovered accidentally, for example when a routine test unexpectedly finds protein in the urine, or when an ultrasound scan happens to find calcium deposits in the kidneys.

Others patients develop kidney stones. Kidney stones can cause pain if they cause a blockage to the flow of urine in the urinary system. This type of pain, known as renal colic, is felt in the back and sides and can move down into the groin. Typically the pain comes in waves, building up over several minutes and then settling down in a repeating cycle.

Even if a patient doesn’t develop kidney stones, there is always an excess of calcium in the urine and calcium gets deposited in the kidney (nephrocalcinosis). Patients with excess calcium in the urine may have increased urine volume and thirst.

Patients with Dent Disease may develop softening of bones (rickets), even though their diet contains good amounts of Vitamin D. Sometimes rickets is mild and only discovered on X-rays. However in some young boys it can be severe and the bones can become painful. If so, walking may be delayed. A small child may stop using a limb, appear to have muscle weakness or cry on being picked up.

Some patients maintain normal kidney function throughout life. However severely affected patients may have deteriorating kidney function. This is made worse if they get stones, which cause blockages to the urinary system. A few patients will require renal replacement therapy, in the form of dialysis or a kidney transplant. It is very rare for this to happen in childhood however.

A small number of patients with what is known as Dent Disease type 2 (see ‘How the disease works’ below) may also have mild learning difficulties and reduced growth rates.

A first step is to confirm the diagnosis. Young people rarely develop kidney stones. If they do it is important to find out what the stone is made of. This is the first step in understanding what is happening. Also it is uncommon to find calcium deposited in the kidney on an ultrasound scan, and further investigation is needed.

In Dent Disease the stones and the nephrocalcinosis are due to too much calcium in the urine. There are many possible reasons for excess calcium in the urine. However, the features that go with Dent Disease are distinctive. Not only is there too much calcium in the urine but there is an excess of certain proteins as well. This pattern of proteins can be identified by a laboratory test of a urine sample. Together these findings point to the diagnosis.

While there is no treatment that corrects the underlying disease process, treatment reduces the symptoms of Dent Disease and improves quality of life. Rickets needs to be prevented or actively treated. This is done with dietary supplements such as vitamin D. Also substances lost in the urine, such as phosphate, bicarbonate or citrate, may need to be supplemented.

A diuretic (water pill) called thiazide may be prescribed to help reduce the loss of calcium in the urine.

Kidney stones may need surgical removal. If so patients are best served by a multidisciplinary team involving expertise in radiology, urology and nephrology.

Pending

The Dent and Lowe Rare Disease Group will hold regular patient and family information days. Details will be advertised here.

Kidneys control the body’s fluids. Blood is continuously filtered in the kidney to produce a watery fluid that is then processed in microscopic kidney tubules. Almost all of this fluid is recovered along with important elements that the body needs. Only a small amount is left containing waste products, and this is urine.

The microscopic tubules of the kidney use different systems to recover different elements from the tubular fluid. One system picks out proteins. It is this system that is defective in Dent Disease. Proteins that are present in the blood stream and are small enough to slip through the kidney filters pass normally into the tubular fluid. If they are not recovered, they are lost in the urine. Some small proteins are important for carrying other substances such as vitamins. If the proteins are lost, the things that they carry are lost too. The body will attempt to make up for the losses by producing more of these proteins.

The same tubular recovery system plays a part in recovering calcium for the body. Therefore in Dent Disease more calcium than normal gets left in the urine. Calcium salts tend to build-up inside the tubules. This is rather like hard water furring up in a kettle. Bit by bit microscopic deposits of calcium build up. They may go on to form a kidney stone that can break free and pass down the urinary tract. Sometimes stones can block the urinary tract. If this persists then kidney damage can occur. Calcium deposits in the tissues of the kidney can also cause local tissue damage in a process that resembles scarring.

How Dent Disease is inherited

Dent Disease is caused by changes in one of two genes – CLCN5 and OCRL. Sometimes, patients with mutations in CLCN5 are referred to as having Dent Disease type 1 and those with mutations in OCRL as having Dent Disease type 2. Both genes occur on the X-chromosome.

Women have two X-chromosome. If a woman has a fault in one X-chromosome gene the other normal gene will compensate. However men have only one X chromosome. (Its partner chromosome is a Y-chromosome that carries different genes). Therefore, if a male has an abnormal gene on his X-chromosome there is no spare copy. The faulty gene will take full effect.

This is why only boys are affected in Dent Disease. Females who have the abnormal gene are extremely unlikely to develop the condition.

The fault in the gene can be inherited or it can occur spontaneously. Where it is inherited, the mother passes it on to her son. The mother is said to be a ‘carrier’. There is a 50% chance of this occurring as she can pass on either the normal or the faulty copy. Her daughters also have a 50% risk of inheriting the faulty copy. They would then be carriers just like their mother. An affected father cannot pass on the disease to his sons as they inherit his Y-chromosome. But he will pass it on to all his daughters who will be carriers of the disease.

This is shown in Figure One below:

The Dent & Lowe Rare Disease Group (RDG) is working with international partners with the aim of finding new and improved treatments, and to empower patients. A first step is to compare the symptoms and genetic markers of Lowe Syndrome. To do this the RDG is registering patients in the National Renal Rare Disease Registry (RaDaR). The registry will be used to find suitable participants for future research trials into the effectiveness of new treatments. If you are interested in finding out more about RaDaR or the activity of the RDG please visit the Dent & Lowe RDG page.