Hypercalcuric Rickets Associated with Renal Tubular Damage

Dent, C. E.; Friedman, M.

doi:10.1136/adc.39.205.240

Cited by 166 publications

(100 citation statements)

References 18 publications

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“…Its clinical characteristics were first described in 1964 by Dent and Friedman [15], and Wrong et al [16] named it ''Dent disease'' in 1994. In 1995, the genetic association of this condition with CLCN5 was identified [17].…”

Section: Discussionmentioning

confidence: 99%

A case of adult Dent disease in Japan with advanced chronic kidney disease

et al. 2013

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Dent disease is an inherited tubulopathy caused by a mutation in the CLCN5 chloride channel gene. In cases of Dent disease in Japan (Japanese Dent, J-Dent), renal function is generally preserved and rarely progresses to advanced kidney dysfunction. However, the long-term prognosis of J-Dent remains unknown. We report the case of a 32-year-old man with J-Dent who developed advanced kidney dysfunction. Since the age of 3 years, he persistently exhibited proteinuria, and examination of a kidney biopsy specimen indicated focal segmental glomerulosclerosis (FSGS)-like lesions. Repeated corticosteroid treatments were found to be ineffective. After the age of 18 years, the patient was lost to follow-up and treatment was discontinued. The patient presented to our hospital again at the age of 32 years with advanced kidney dysfunction with low-molecularweight proteinuria (LMWP), along with proximal tubular dysfunction and nephrocalcinosis. The patient's 5-yearold nephew was also found to have LMWP from the age of 7 months. Therefore, Dent disease was suspected and genetic testing in the patient and his nephew revealed a CLCN5 mutation. Our case report suggests that J-Dent may cause advanced kidney dysfunction in adulthood, and, therefore, close collaboration between pediatricians and nephrologists is essential for the early identification of this complication. When male patients exhibit chronic kidney disease (CKD) of unknown etiology along with proximal tubular dysfunction and nephrocalcinosis, Dent disease should be considered. Investigations of undiagnosed adult J-Dent cases and further research on the natural history of J-Dent will help us better understand its clinical characteristics, prognosis, and effective treatment options.Keywords CLCN5 Á Dent disease Á Focal segmental glomerulosclerosis Á Japanese Dent (J-Dent) Á Low-molecular-weight proteinuria (LMWP) Abbreviations LMWP Low-molecular-weight proteinuria XRN X-linked recessive nephrolithiasis XLHR X-linked recessive hypophosphatemic rickets FSGS Focal segmental glomerulosclerosis

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Section: Discussionmentioning

confidence: 99%

A case of adult Dent disease in Japan with advanced chronic kidney disease

et al. 2013

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“…This condition, also referred to as "Lowe syndrome," is a severe X-linked disorder characterized by congenital cataracts (12), kidney readsorption defects caused by proximal tubule dysfunction, cognitive impairment, muscle hypotonia, and autism spectrum behavioral disorders (13,14). The other condition is Dent disease, an X-linked disorder involving kidney defects very similar to those associated with Lowe syndrome but, for reasons not yet known, few other dysfunctions (15)(16)(17)(18)(19).OCRL comprises an N-terminal Pleckstrin Homology (PH) domain followed in sequence by a central inositol 5′-phosphatase domain, an ASPM-SPD-2-Hydin (ASH) domain, and a catalytically inactive RhoGAP (GTPase Activating Protein)-like domain (20). OCRL interacts with several endocytic proteins, including clathrin (20-23), the clathrin adaptor AP2 (21, 24), and several endocytic (e. g., Rab5) (25, 26) and nonendocytic Rab GTPases (20, 26, 27).…”

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confidence: 99%

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confidence: 99%

Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1

Swan

Tomasini

Pirruccello

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

117

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Mutations of the inositol 5′ phosphatase oculocerebrorenal syndrome of Lowe (OCRL) give rise to the congenital X-linked disorders oculocerebrorenal syndrome of Lowe and Dent disease, two conditions giving rise to abnormal kidney proximal tubule reabsorption, and additional nervous system and ocular defects in the case of Lowe syndrome. Here, we identify two closely related endocytic proteins, Ses1 and Ses2, which interact with the ASH-RhoGAP-like (ASPM-SPD-2-Hydin homology and Rho-GTPase Activating Domain-like) domain of OCRL. The interaction is mediated by a short amino acid motif similar to that used by the rab-5 effector APPL1 (Adaptor Protein containing pleckstrin homology [PH] domain, PTB domain and Leucine zipper motif 1) APPL1 for OCRL binding. Ses binding is mutually exclusive with APPL1 binding, and is disrupted by the same missense mutations in the ASHRhoGAP-like domain that also disrupt APPL1 binding. Like APPL1, Ses1 and -2 are localized on endosomes but reside on different endosomal subpopulations. These findings define a consensus motif (which we have called a phenylalanine and histidine [F&H] motif) for OCRL binding and are consistent with a scenario in which Lowe syndrome and Dent disease result from perturbations at multiple sites within the endocytic pathway.Dent disease | endocytosis | Lowe syndrome I nositol phospholipids play a critical regulatory function in cell physiology, including membrane traffic. The interconversion of different phosphoinositide species via the action of kinases and phosphatases plays a key role in the maturation and progression of membranes through different stations of the exocytic and endocytic pathways, coordinating these processes with signaling reactions. Thus, the correct spatial and temporal regulation of these enzymes is of central importance (1, 2). As a consequence, not only the lack of these enzymes but also the disruption of their interactions can have profound effects on cell function and result in pathological conditions (2-9).Two human diseases are caused by mutations in an enzyme that selectively dephosphorylates the inositol ring at the 5′ position, using phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P 3 ], two phosphoinositides concentrated in the plasma membrane, as its preferred substrates (10). One such disease is oculocerebrorenal syndrome of Lowe (hence the enzyme name "OCRL") (3, 11). This condition, also referred to as "Lowe syndrome," is a severe X-linked disorder characterized by congenital cataracts (12), kidney readsorption defects caused by proximal tubule dysfunction, cognitive impairment, muscle hypotonia, and autism spectrum behavioral disorders (13,14). The other condition is Dent disease, an X-linked disorder involving kidney defects very similar to those associated with Lowe syndrome but, for reasons not yet known, few other dysfunctions (15)(16)(17)(18)(19).OCRL comprises an N-terminal Pleckstrin Homology (PH) domain followed in sequence by a central inositol 5′-phospha...

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“…At that time, they identified this disease as a form of Fanconis syndrome due to impairment of renal acidification similar to that observed in such patients (15). Besides the renal acidification impairment, Dents disease patients also exhibited rickets, hypercalciuria, nephrocalcinosis, low molecular weight (LMW) proteinuria, and nephrolithiasis (14)(15)(16)(17). Progressive renal failure may occur in the late stages of Dents disease (14,16,17).…”

Section: Is Nephrolithiasis a Matter Of Imbalances In Mineral Metabolmentioning

confidence: 59%

“…Alkaline urine is a common sign found in Fanconis syndrome patients (15). Although Dents disease is currently characterized as an independent pathology, a urine acidification disorder was also found in some patients (13)(14)(15)(16)(17).…”

Section: Clc-5 Chloride Channel and Urine Acidificationmentioning

confidence: 99%

ClC-5 chloride channel and kidney stones: what is the link?

Silva

Morales

Lopes

2001

Braz J Med Biol Res

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Nephrolithiasis is one of the most common diseases in the Western world. The disease manifests itself with intensive pain, sporadic infections, and, sometimes, renal failure. The symptoms are due to the appearance of urinary stones (calculi) which are formed mainly by calcium salts. These calcium salts precipitate in the renal papillae and/ or within the collecting ducts. Inherited forms of nephrolithiasis related to chromosome X (X-linked hypercalciuric nephrolithiasis or XLN) have been recently described. Hypercalciuria, nephrocalcinosis, and male predominance are the major characteristics of these diseases. The gene responsible for the XLN forms of kidney stones was cloned and characterized as a chloride channel called ClC-5. The ClC-5 chloride channel belongs to a superfamily of voltage-gated chloride channels, whose physiological roles are not completely understood. The objective of the present review is to identify recent advances in the molecular pathology of nephrolithiasis, with emphasis on XLN. We also try to establish a link between a chloride channel like ClC-5, hypercalciuria, failure in urine acidification and protein endocytosis, which could explain the symptoms exhibited by XLN patients.

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Hypercalcuric Rickets Associated with Renal Tubular Damage

Cited by 166 publications

References 18 publications

A case of adult Dent disease in Japan with advanced chronic kidney disease

A case of adult Dent disease in Japan with advanced chronic kidney disease

Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1

ClC-5 chloride channel and kidney stones: what is the link?

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