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Dent disease type 2(DENT2)

MedGen UID:
Concept ID:
Disease or Syndrome
Synonym: Dent Disease 2
SNOMED CT: Dent disease type 2 (717790004)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
Concept ID:
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
Gene (location): OCRL (Xq26.1)
Monarch Initiative: MONDO:0010359
OMIM®: 300555
Orphanet: ORPHA93623

Disease characteristics

Excerpted from the GeneReview: Dent Disease
Dent disease, an X-linked disorder of proximal renal tubular dysfunction, is characterized by low molecular weight (LMW) proteinuria, hypercalciuria, and at least one additional finding including nephrocalcinosis, nephrolithiasis, hematuria, hypophosphatemia, chronic kidney disease (CKD), and evidence of X-linked inheritance. Males younger than age ten years may manifest only LMW proteinuria and/or hypercalciuria, which are usually asymptomatic. Thirty to 80% of affected males develop end-stage renal disease (ESRD) between ages 30 and 50 years; in some instances ESRD does not develop until the sixth decade of life or later. The disease may also be accompanied by rickets or osteomalacia, growth restriction, and short stature. Disease severity can vary within the same family. Males with Dent disease 2 (caused by pathogenic variants in OCRL) may also have mild intellectual disability, cataracts, and/or elevated muscle enzymes. Due to random X-chromosome inactivation, some female carriers may manifest hypercalciuria and, rarely, renal calculi and moderate LMW proteinuria. Females rarely develop CKD. [from GeneReviews]
John C Lieske  |  Dawn S Milliner  |  Lada Beara-Lasic, et. al.   view full author information

Additional descriptions

Dent disease-2 (DENT2) is an X-linked disorder of renal tubular epithelial function in which all of the clinical findings may be traced to impaired reabsorption of filtered solutes. Characteristic abnormalities include low molecular weight proteinuria and other features of Fanconi syndrome (see 134600), such as glycosuria, aminoaciduria, and phosphaturia, but typically do not include proximal renal tubular acidosis. Progressive renal failure is common, as are nephrocalcinosis and kidney stones (summary by Hoopes et al., 2005). For a discussion of genetic heterogeneity of Dent disease, see 300009.  http://www.omim.org/entry/300555
From MedlinePlus Genetics
Dent disease is a chronic kidney disorder that occurs almost exclusively in males. In affected individuals, kidney problems result from damage to structures called proximal tubules. Signs and symptoms of this condition appear in early childhood and worsen over time.

The most frequent sign of Dent disease is the presence of an abnormally large amount of proteins in the urine (tubular proteinuria). Other common signs of the disorder include excess calcium in the urine (hypercalciuria), calcium deposits in the kidneys (nephrocalcinosis), and kidney stones (nephrolithiasis). Kidney stones can cause abdominal pain and blood in the urine (hematuria). In most affected males, progressive kidney problems lead to end-stage renal disease (ESRD) in early to mid-adulthood. ESRD is a life-threatening failure of kidney function that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively.

Some people with Dent disease develop rickets, a bone disorder that results when the levels of vitamin D and certain minerals (including calcium) in the blood become too low. Rickets can be associated with weakening and softening of the bones, bone pain, bowed legs, and difficulty walking.

Researchers have described two forms of Dent disease, which are distinguished by their genetic cause and pattern of signs and symptoms. Both forms of Dent disease (type 1 and type 2) are characterized by the features described above, but Dent disease 2 can also be associated with abnormalities unrelated to kidney function. These additional signs and symptoms include mild intellectual disability, weak muscle tone (hypotonia), and clouding of the lens of the eyes (cataract) that is described as subclinical because it does not impair vision. Some researchers consider Dent disease 2 to be a mild variant of a similar disorder called Lowe syndrome.  https://medlineplus.gov/genetics/condition/dent-disease

Clinical features

From HPO
MedGen UID:
Concept ID:
Abnormally high level of calcium in the urine.
MedGen UID:
Concept ID:
Disease or Syndrome
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
MedGen UID:
Concept ID:
Disease or Syndrome
An increased concentration of an amino acid in the urine.
Chronic kidney disease
MedGen UID:
Concept ID:
Disease or Syndrome
Functional anomaly of the kidney persisting for at least three months.
Proximal tubulopathy
MedGen UID:
Concept ID:
Disease or Syndrome
Dysfunction of the proximal tubule, which is the portion of the duct system of the nephron of the kidney which leads from Bowman's capsule to the loop of Henle.
Low-molecular-weight proteinuria
MedGen UID:
Concept ID:
Excretion in urine of proteins of a size smaller than albumin (molecular weight 69 kD).
Short stature
MedGen UID:
Concept ID:
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Cognitive impairment
MedGen UID:
Concept ID:
Mental or Behavioral Dysfunction
Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.
Mild global developmental delay
MedGen UID:
Concept ID:
A mild delay in the achievement of motor or mental milestones in the domains of development of a child.
Umbilical hernia
MedGen UID:
Concept ID:
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
MedGen UID:
Concept ID:
Disease or Syndrome
An abnormally decreased phosphate concentration in the blood.
Elevated circulating aspartate aminotransferase concentration
MedGen UID:
Concept ID:
The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal.
Elevated circulating alanine aminotransferase concentration
MedGen UID:
Concept ID:
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
Elevated circulating creatine kinase concentration
MedGen UID:
Concept ID:
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Increased circulating lactate dehydrogenase concentration
MedGen UID:
Concept ID:
An elevated level of the enzyme lactate dehydrogenase in the blood circulation.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Dent disease type 2 in Orphanet.

Professional guidelines


Thaventhiran JED, Lango Allen H, Burren OS, Rae W, Greene D, Staples E, Zhang Z, Farmery JHR, Simeoni I, Rivers E, Maimaris J, Penkett CJ, Stephens J, Deevi SVV, Sanchis-Juan A, Gleadall NS, Thomas MJ, Sargur RB, Gordins P, Baxendale HE, Brown M, Tuijnenburg P, Worth A, Hanson S, Linger RJ, Buckland MS, Rayner-Matthews PJ, Gilmour KC, Samarghitean C, Seneviratne SL, Sansom DM, Lynch AG, Megy K, Ellinghaus E, Ellinghaus D, Jorgensen SF, Karlsen TH, Stirrups KE, Cutler AJ, Kumararatne DS, Chandra A, Edgar JDM, Herwadkar A, Cooper N, Grigoriadou S, Huissoon AP, Goddard S, Jolles S, Schuetz C, Boschann F; Primary Immunodeficiency Consortium for the NIHR Bioresource, Lyons PA, Hurles ME, Savic S, Burns SO, Kuijpers TW, Turro E, Ouwehand WH, Thrasher AJ, Smith KGC
Nature 2020 Jul;583(7814):90-95. Epub 2020 May 6 doi: 10.1038/s41586-020-2265-1. PMID: 32499645Free PMC Article
Slayton RL
Pediatr Dent 2015 Mar-Apr;37(2):106-10. PMID: 25905650
Aimetti M
Int J Esthet Dent 2014 Summer;9(2):251-67. PMID: 24765632

Recent clinical studies


Ye Q, Shen Q, Rao J, Zhang A, Zheng B, Liu X, Shen Y, Chen Z, Wu Y, Hou L, Jian S, Wei M, Ma M, Sun S, Li Q, Dang X, Wang Y, Xu H, Mao J; for Chinese Children Genetic Kidney Disease Database (CCGKDD), “Internet Plus” Nephrology Alliance of National Center for Children's Care
Clin Genet 2020 Mar;97(3):407-417. Epub 2020 Jan 13 doi: 10.1111/cge.13663. PMID: 31674016


Motoyoshi Y, Yabuuchi T, Miura K, Hattori M, Kiyohara K
CEN Case Rep 2022 Aug;11(3):366-370. Epub 2022 Jan 31 doi: 10.1007/s13730-022-00685-3. PMID: 35098431Free PMC Article
Ye Q, Shen Q, Rao J, Zhang A, Zheng B, Liu X, Shen Y, Chen Z, Wu Y, Hou L, Jian S, Wei M, Ma M, Sun S, Li Q, Dang X, Wang Y, Xu H, Mao J; for Chinese Children Genetic Kidney Disease Database (CCGKDD), “Internet Plus” Nephrology Alliance of National Center for Children's Care
Clin Genet 2020 Mar;97(3):407-417. Epub 2020 Jan 13 doi: 10.1111/cge.13663. PMID: 31674016
Bökenkamp A, Ludwig M
Pediatr Nephrol 2016 Dec;31(12):2201-2212. Epub 2016 Mar 24 doi: 10.1007/s00467-016-3343-3. PMID: 27011217Free PMC Article

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