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Disease Profile

Dent disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Dent's disease; Dents disease; Dent syndrome;

Summary

Dent disease is a chronic kidney disease that primarily affects males. While symptoms and severity vary, they usually begin in childhood and worsen over time. The most common feature of Dent disease is proteinuria (protein in the urine). Other common features include excess calcium in the urine (hypercalciuria); calcium deposits in the kidneys (nephrocalcinosis); and kidney stones.[1] Less common features include rickets and mildy short stature. Progressive kidney problems often lead to kidney failure by early to mid-adulthood.[1][2]

There are two forms of Dent disease which are distinguished based on their genetic causes. Both forms are inherited in an X-linked recessive manner.[1]

  • Dent disease type 1 is caused by a mutation in the CLCN5 gene.
  • Dent disease type 2 is caused by a mutation in the OCRL gene. Males with this form are also at increased risk for mild intellectual disability and hypotonia.[1][2]

Treatment is based on the symptoms present, aiming to delay progression of kidney disease and improve quality of life.[2]

Symptoms

The specific symptoms and severity of Dent disease can vary greatly, even among members of the same family.[3] Signs of Dent disease usually appear in childhood and worsen over time. Common signs of Dent disease include:

  • a large amount of protein in the urine (proteinuria)
  • excess calcium in the urine (hypercalciuria)
  • calcium deposits in the kidneys (nephrocalcinosis)
  • kidney stones which may cause abdominal pain and blood in the urine (hematuria)

Less commonly, people with Dent disease develop rickets, a bone disorder due to low levels of vitamin D and certain minerals in the blood. Rickets can be associated with weakening of the bones, bone pain, bowed legs, and difficulty walking.[1]

Most affected males experience progressive kidney problems that lead to end-stage renal disease (kidney failure) in early to mid-adulthood.

Some people with Dent disease have features that affect other organ systems, such as mild intellectual impairment, weak muscle tone (hypotonia) and cataracts. The occurrence of these features, when caused by a mutation in the OCRL gene, is referred to as Dent disease type 2.[4]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Aminoaciduria
High urine amino acid levels
Increased levels of animo acids in urine

[ more ]

0003355
Chronic kidney disease
0012622
Focal segmental glomerulosclerosis
0000097
Glycosuria
Glucose in urine
0003076
Hematuria
Blood in urine
0000790
High serum calcitriol
0031415
Hypercalciuria
Elevated urine calcium levels
0002150
Hyperphosphaturia
High urine phosphate levels
0003109
Hyperuricosuria
High urine uric acid level
0003149
Low-molecular-weight proteinuria
0003126
Nephrolithiasis
Kidney stones
0000787
Non-acidotic proximal tubulopathy
0005574
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures

[ more ]

0002757
Renal hypophosphatemia
0008732
Renal phosphate wasting
0000117
Renal tubular atrophy
0000092
Tubulointerstitial fibrosis
0005576
30%-79% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain

[ more ]

0002027
Bone pain
0002653
Elevated serum creatine kinase
Elevated blood creatine phosphokinase
Elevated circulating creatine phosphokinase
Elevated creatine kinase
Elevated serum CPK
Elevated serum creatine phosphokinase
High serum creatine kinase
Increased CPK
Increased creatine kinase
Increased creatine phosphokinase
Increased serum CK
Increased serum creatine kinase
Increased serum creatine phosphokinase

[ more ]

0003236
Nephrocalcinosis
Too much calcium deposited in kidneys
0000121
5%-29% of people have these symptoms
Bowing of the legs
Bowed legs
Bowed lower limbs

[ more ]

0002979
Bulging epiphyses
Bulging end part of bone
0003013
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Delayed epiphyseal ossification
0002663
Enlargement of the ankles
0003029
Enlargement of the wrists
0003020
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation

[ more ]

0001256
Metaphyseal irregularity
Irregular wide portion of a long bone
0003025
Mild global developmental delay
0011342
Muscular hypotonia
Low or weak muscle tone
0001252
Osteomalacia
Softening of the bones
0002749
Rickets
Weak and soft bones
0002748
Sparse bone trabeculae
0002752
Thin bony cortex
0002753

Cause

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.[1]

Diagnosis

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:

  • 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
  • Hypercalciuria (excessive calcium in the urine)
  • At least one of the following:

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.[2]

Treatment

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.[2]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Social Networking Websites

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • Genetics Home Reference (GHR) contains information on Dent disease. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
        • The Renal Association has a website that provides comprehensive information about its rare disease initiative and information for patients about Dent disease.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Dent disease in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Dent disease. Click on the link to view a sample search on this topic.

            References

            1. Dent disease. Genetics Home Reference. September, 2012; https://ghr.nlm.nih.gov/condition/dent-disease.
            2. John C Lieske, Dawn S Milliner, Lada Beara-Lasic, Peter Harris, Katharina Hopp, Andrea Cogal, and Kari Mattison. Dent Disease. GeneReviews. September, 2014; https://www.ncbi.nlm.nih.gov/books/NBK99494/.
            3. Dent Disease. NORD. 2014; https://rarediseases.org/rare-diseases/dent-disease/.
            4. Devuyst O, Thakker RV. Dent's disease. Orphanet J Rare Dis. October 14, 2010; 5:28:

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