What is Dent Disease?
Dent disease is a rare genetic kidney disorder that affects males almost exclusively.
Symptoms usually appear during childhood, but some individuals may be undiagnosed well into adulthood.
Who is Affected by Dent Disease?
In most cases, male children inherit the disorder from a carrier mother who has extremely mild symptoms of the disease, if any at all. When a mother is a known carrier of the CLCN5 or the OCRL1 mutation, there is a 50 percent chance of passing that mutation on to her children of either gender. Males who inherited a mutation will have the disorder and pass it to their daughters, but not their sons; females who inherited the mutation will be carriers.
X-linked recessive inheritance pattern
Types of
Dent Disease
Dent disease type 1 is caused by changes (mutations) in the CLCN5 gene.
Dent disease type 2 is caused by mutations in the OCRL1 gene. Individuals may have additional symptoms with Dent type 2, including mild intellectual disability, eye involvement or diminished muscle tone (hypotonia).
These mutations may be inherited or occur randomly with no previous family history of the disorder (spontaneously) called a de novo mutation.
Some individuals who meet strict clinical criteria for Dent do not have mutations in either the CLCN5 or OCRL1 genes, suggesting that additional subtypes of Dent disease caused by mutations in as yet unidentified genes most likely exist.
Dent Disease
symptoms
Low-molecular-weight proteinuria
Elevated levels of proteins and calcium in the urine (proteinuria and hypercalciuria). The type of proteinuria seen in Dent disease is known as low-molecular-weight proteinuria, which is a characteristic finding of the disorder and not always detected in routine medical testing. Hypercalciuria and low molecular weight proteinuria may be the only symptoms that develop in some people.
Kidney calcifications (nephrocalcinosis) or kidney stones (nephrolithiasis)
Chronic kidney disease with a progressive decline in kidney function
Renal failure
Usually does not occur until 30 to 50 years of age or later and may not occur at all in some individuals.
Other symptoms
Some individuals with Dent disease may also develop a bone disease, such as softening of the bones (osteomalacia) and hypophosphatemic rickets.
Some individuals with Dent disease have developed vitamin A deficiency, which can lead to impaired night vision and dry eyes (xerophthalmia).
Some individuals with Dent disease Type 2 have developed additional symptoms, including mild intellectual disability, hypotonia, and clouding of the lenses of the eyes (cataracts).
Diagnosis & current treatments
Diagnosis
A clinical diagnosis of Dent disease is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. A diagnosis may be suspected in individuals with high levels of low-molecular-weight proteins in the urine, excess levels of calcium in the urine, and one of the following: kidney calcifications, kidney stones, blood in the urine, low phosphates, chronic kidney disease, or evidence of X-linked recessive inheritance.
Testing options
Molecular genetic testing is generally recommended, since it is becoming increasingly recognized that other genetic causes of nephrocalcinosis and chronic kidney disease share clinical features with Dent disease.
Clinical tests that can be done, while awaiting genetic testing include:
- Low molecular-weight (LMW) proteinuria at least five times above the upper limit of normal (the pathognomonic finding of Dent disease).
- No known cases of Dent disease have been missed using this screening.
- Elevated urinary excretion of Beta 2 microglobulin.
- Urinalysis”assessing for protein and blood.
Join the Mayo Clinic’s Dent disease registry by emailing rarekidneystones@mayo.edu or calling 1-800-270-4637.
Current treatment
There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of these diseases, there are no treatment trials that have been tested on a large group of patients.
Dent disease treatment is directed toward the specific symptoms that are apparent in each individual. In order to preserve kidney function, lifestyle changes can/should include: a low-salt diet, maintaining hydration, taking medication to prevent kidney stones, taking supplements, and avoiding medications that can harm the kidneys, such as NSAIDS – Non Steroidal Anti-Inflammatories—like Advil, Aleve, Ibuprofen, Naproxen, etc.) and certain antibiotics. Be cautious of contrast dyes in diagnostic tests such as CT scans, MRI’s, and angiograms. Always let your doctor know that you or your loved one has Dent disease so they can be sure that the medication or test being prescribed does not have an associated toxic effect on your kidneys. In some cases, dialysis or a transplant may be needed.
