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dent_disease [2026/07/06 03:35] – [Eye Findings] Scott Larsondent_disease [2026/07/06 03:37] (current) – Scott Larson
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 ===== Other Findings ===== ===== Other Findings =====
  
-  * **Rickets or osteomalacia:** Due to low vitamin D and mineral levels; responds to vitamin D supplementation and phosphorus repletion.* +  * **Rickets or osteomalacia:** Due to low vitamin D and mineral levels; responds to vitamin D supplementation and phosphorus repletion. 
-  * **Growth restriction and short stature:** May be treated with human growth hormone without adversely affecting kidney function.* +  * **Growth restriction and short stature:** May be treated with human growth hormone without adversely affecting kidney function. 
-  * **Mild intellectual disability:** Seen in some males with Dent disease 2 (OCRL mutations).* +  * **Mild intellectual disability:** Seen in some males with Dent disease 2 (OCRL mutations). 
-  * **Hypotonia (weak muscle tone):** Associated with Dent disease 2.* +  * **Hypotonia (weak muscle tone):** Associated with Dent disease 2. 
-  * **Elevated muscle enzymes:** May be present in Dent disease 2.* +  * **Elevated muscle enzymes:** May be present in Dent disease 2. 
-  * **Female carriers:** Due to random X-chromosome inactivation, some may manifest hypercalciuria and, rarely, renal calculi and moderate LMWP. Females rarely develop CKD.*+  * **Female carriers:** Due to random X-chromosome inactivation, some may manifest hypercalciuria and, rarely, renal calculi and moderate LMWP. Females rarely develop CKD.
  
 **Management** is supportive: **Management** is supportive:
  
-  * Thiazide diuretics may decrease urinary calcium excretion but are limited by side effects (hypokalemia, volume depletion).* +  * Thiazide diuretics may decrease urinary calcium excretion but are limited by side effects (hypokalemia, volume depletion). 
-  * ACE inhibitors/ARBs have unclear effectiveness for Dent disease-associated proteinuria.* +  * ACE inhibitors/ARBs have unclear effectiveness for Dent disease-associated proteinuria. 
-  * Avoid renal toxins (NSAIDs, aminoglycosides, IV contrast agents).* +  * Avoid renal toxins (NSAIDs, aminoglycosides, IV contrast agents). 
-  * Monitor annually: urinary calcium, GFR, blood pressure, hematocrit, serum calcium and phosphorus.* +  * Monitor annually: urinary calcium, GFR, blood pressure, hematocrit, serum calcium and phosphorus. 
-  * Renal replacement therapy (hemodialysis, peritoneal dialysis, or transplantation) for ESRD. The disease does not recur after transplantation.*+  * Renal replacement therapy (hemodialysis, peritoneal dialysis, or transplantation) for ESRD. The disease does not recur after transplantation.
  
 ===== Etiology ===== ===== Etiology =====
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 Dent disease is an **X-linked recessive** disorder caused by mutations in one of two genes: Dent disease is an **X-linked recessive** disorder caused by mutations in one of two genes:
  
-  * **Dent disease 1 (~60% of cases):** Caused by mutations in the **CLCN5** gene (chromosome Xp11.22), which encodes the electrogenic chloride/proton exchanger ClC-5. ClC-5 is predominantly expressed in the proximal tubule and controls acidification and recycling of endosomal compartments. Loss of ClC-5 function impairs megalin-mediated endocytic reabsorption of low-molecular-weight proteins.* +  * **Dent disease 1 (~60% of cases):** Caused by mutations in the **CLCN5** gene (chromosome Xp11.22), which encodes the electrogenic chloride/proton exchanger ClC-5. ClC-5 is predominantly expressed in the proximal tubule and controls acidification and recycling of endosomal compartments. Loss of ClC-5 function impairs megalin-mediated endocytic reabsorption of low-molecular-weight proteins. 
-  * **Dent disease 2 (~15% of cases):** Caused by mutations in the **OCRL** gene (chromosome Xq25), which encodes a phosphatidylinositol-4,5-bisphosphate 5-phosphatase (OCRL1). OCRL mutations are also responsible for Lowe syndrome; Dent disease 2 is considered a milder phenotypic variant. Both ClC-5 and OCRL1 participate in a common endocytic pathway in the proximal tubule.* +  * **Dent disease 2 (~15% of cases):** Caused by mutations in the **OCRL** gene (chromosome Xq25), which encodes a phosphatidylinositol-4,5-bisphosphate 5-phosphatase (OCRL1). OCRL mutations are also responsible for Lowe syndrome; Dent disease 2 is considered a milder phenotypic variant. Both ClC-5 and OCRL1 participate in a common endocytic pathway in the proximal tubule. 
-  * **Remaining ~25% of cases:** The genetic cause is unknown, suggesting involvement of additional genes.*+  * **Remaining ~25% of cases:** The genetic cause is unknown, suggesting involvement of additional genes.
  
 There is considerable intra-familial variability in disease severity, and no clear genotype-phenotype correlation has been established, although mutations affecting the pore or CBS domains of ClC-5 may be associated with more frequent GFR decline. There is considerable intra-familial variability in disease severity, and no clear genotype-phenotype correlation has been established, although mutations affecting the pore or CBS domains of ClC-5 may be associated with more frequent GFR decline.
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   - MedlinePlus. Dent disease. National Library of Medicine. [[https://medlineplus.gov/genetics/condition/dent-disease/]]   - MedlinePlus. Dent disease. National Library of Medicine. [[https://medlineplus.gov/genetics/condition/dent-disease/]]
  
 +{{tag>syndrome}}