Dent disease

What causes Dent disease?

Mutations in the CLCN5 gene cause Dent disease type 1 (60% of cases), and mutations in the OCRL gene cause Dent disease type 2 (15% of cases). In the remaining 25% of cases, the genetic cause is unknown.

The CLCN5 and OCRL genes give the body instructions to make proteins needed for normal kidney function - particularly the function of the proximal tubules. The proximal tubules help to reabsorb nutrients, water, and other substances that have been filtered from the bloodstream. Studies suggest that mutations in these genes impair the ability of the proximal tubules to reabsorb, leading to the kidney problems in people with Dent disease.

Last updated on 05-01-20

How is Dent disease diagnosed?

A diagnosis of Dent disease is suspected in people with the following 3 criteria, when there is no other known cause of proximal tubule dysfunction:

A possible diagnosis of Dent disease is considered if LMW proteinuria and at least one other finding are present.

In 75% of males with the above criteria, genetic testing confirms the diagnosis by finding a mutation in the CLCN5 (Dent disease 1) or OCRL (Dent disease 2) gene. About 25% of people with a clinical diagnosis of Dent disease do not have a mutation in either of these genes, suggesting that other, yet unidentified genes may also cause the condition.

Last updated on 05-01-20

How is Dent disease inherited?

The inheritance of Dent disease is X-linked recessive. X-linked recessive conditions usually occur in males, who only have one X chromosome (and one Y chromosome). Females have two X chromosomes, so if they have a gene mutation on one of them, they still have a normal copy on their other X chromosome. For this reason, females are typically unaffected. A female with one mutated gene responsible for an X-linked recessive condition is referred to as a carrier. While females can have an X-linked recessive condition, it is very rare.

If a mother is a carrier of an X-linked recessive condition and the father is not, the risk to children depends on each child's sex.

  • Each male child has a 50% chance to be unaffected, and a 50% chance to be affected
  • Each daughter has a 50% chance to be unaffected, and a 50% chance to be an unaffected carrier

If a father has the condition and the mother is not a carrier, all sons will be unaffected, and all daughters will be carriers.

Due to random X-chromosome inactivation, some female carriers may have hypercalciuria (and rarely renal calculi and moderate LMW proteinuria). Females rarely, if ever, develop chronic kidney disease.

Last updated on 05-01-20

How might Dent disease be treated?

No standard guidelines have been established for the treatment of Dent disease. The main goals of treatment are to decrease hypercalciuria, prevent kidney stones and nephrocalcinosis, and delay the progression of chronic kidney disease (CKD).

Thiazide diuretics in doses greater than 0.4 mg/kg/day have decreased urinary calcium excretion by more than 40% in boys with Dent disease. However, frequent side effects included hypokalemia, volume depletion, and cramping. Careful dosing and close monitoring for these side effects are necessary.

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been used in children with proteinuria to prevent or delay further loss of kidney function. However, their effectiveness has not been clear.

Although a high citrate diet has been used in the treatment of Dent disease (aiming to slow progression of CKD), no human trials have proven its effectiveness.

If males with Dent disease progress to end-stage renal disease (kidney failure), renal replacement therapy becomes necessary. Hemodialysis, peritoneal dialysis, and renal transplantation are appropriate options. Because Dent disease features are largely localized in the kidney, the disease will not recur.

Last updated on 05-01-20

Where To Start

The Renal Association

The Renal Association has a website that provides comprehensive information about its rare disease initiative and information for patients about Dent disease.

Last updated on 04-27-20

Name: National Kidney Foundation 30 East 33rd Street
New York, NY, 10016, United States
Phone: 212-889-2210 Toll Free: 800-622-9010 Fax : 212-689-9261 Email: info@kidney.org Url: https://www.kidney.org/
Name: American Association of Kidney Patients 3505 E. Frontage Rd., Suite 315
Tampa, FL, 33607-1796, United States
Phone: 813-636-8100 Toll Free: 800-749-2257 Fax : 813-636-8122 Email: info@aakp.org Url: http://www.aakp.org
Name: The Kidney Foundation of Canada 700-15 Gervais Drive Toronto Ontario M3C 1Y8
Canada
Phone: 416-445-0373 Toll Free: 800-387-4474 Fax : 416-445-7440 Email: kidney@kidney.on.ca Url: http://www.kidney.on.ca
Name: American Kidney Fund, Inc. 6110 Executive Boulevard Suite 1010
Rockville, MD, 20852, United States
Phone: 301-881-3052 Toll Free: 866-300-2900 Email: helpline@kidneyfund.org Url: http://www.kidneyfund.org
Name: National Kidney Federation NKF The Point Shireoaks
Coach Road Worksop Notts S81 8BW
United Kingdom
Phone: 0845 601 02 09 Url: http://www.kidney.org.uk/
Name: Dent Disease Foundation Email: caforrest@dentdisease.com Url: http://dentdisease.com

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The RareGuru disease database is regularly updated using data generously provided by GARD, the United States Genetic and Rare Disease Information Center.

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