Dent-2 disease with a Bartter-like phenotype caused by the Asp631Glu mutation in the OCRL gene
Abstract Background Dent disease is an X-linked disorder characterized by low molecular weight proteinuria (LMWP), hypercalciuria, nephrolithiasis and chronic kidney disease (CKD). It is caused by mutations in the chloride voltage-gated channel 5 (CLCN5) gene (Dent disease-1), or in the OCRL gene (D...
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | BMC Nephrology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12882-022-02812-9 |
| _version_ | 1828202559607668736 |
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| author | Eleni Drosataki Sevasti Maragkou Kleio Dermitzaki Ioanna Stavrakaki Dimitra Lygerou Helen Latsoudis Christos Pleros Ioannis Petrakis Ioannis Zaganas Kostas Stylianou |
| author_facet | Eleni Drosataki Sevasti Maragkou Kleio Dermitzaki Ioanna Stavrakaki Dimitra Lygerou Helen Latsoudis Christos Pleros Ioannis Petrakis Ioannis Zaganas Kostas Stylianou |
| author_sort | Eleni Drosataki |
| collection | DOAJ |
| description | Abstract Background Dent disease is an X-linked disorder characterized by low molecular weight proteinuria (LMWP), hypercalciuria, nephrolithiasis and chronic kidney disease (CKD). It is caused by mutations in the chloride voltage-gated channel 5 (CLCN5) gene (Dent disease-1), or in the OCRL gene (Dent disease-2). It is associated with chronic metabolic acidosis; however metabolic alkalosis has rarely been reported. Case presentation We present a family with Dent-2 disease and a Bartter-like phenotype. The main clinical problems observed in the proband included a) primary phosphaturia leading to osteomalacia and stunted growth; b) elevated serum calcitriol levels, leading to hypercalcemia, hypercalciuria, nephrolithiasis and nephrocalcinosis; c) severe salt wasting causing hypotension, hyperaldosteronism, hypokalemia and metabolic alkalosis; d) partial nephrogenic diabetes insipidus attributed to hypercalcemia, hypokalemia and nephrocalcinosis; e) albuminuria, LMWP. Phosphorous repletion resulted in abrupt cessation of hypercalciuria and significant improvement of hypophosphatemia, physical stamina and bone histology. Years later, he presented progressive CKD with nephrotic range proteinuria attributed to focal segmental glomerulosclerosis (FSGS). Targeted genetic analysis for several phosphaturic diseases was unsuccessful. Whole Exome Sequencing (WES) revealed a c.1893C > A variant (Asp631Glu) in the OCRL gene which was co-segregated with the disease in male family members. Conclusions We present the clinical characteristics of the Asp631Glu mutation in the OCRL gene, presenting as Dent-2 disease with Bartter-like features. Phosphorous repletion resulted in significant improvement of all clinical features except for progressive CKD. Angiotensin blockade improved proteinuria and stabilized kidney function for several years. Graphical abstract |
| first_indexed | 2024-04-12T11:51:04Z |
| format | Article |
| id | doaj.art-f39bef399aa44cc9be56f260ffa08b2a |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-04-12T11:51:04Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-f39bef399aa44cc9be56f260ffa08b2a2022-12-22T03:34:11ZengBMCBMC Nephrology1471-23692022-05-012311710.1186/s12882-022-02812-9Dent-2 disease with a Bartter-like phenotype caused by the Asp631Glu mutation in the OCRL geneEleni Drosataki0Sevasti Maragkou1Kleio Dermitzaki2Ioanna Stavrakaki3Dimitra Lygerou4Helen Latsoudis5Christos Pleros6Ioannis Petrakis7Ioannis Zaganas8Kostas Stylianou9Nephrology Department, Heraklion University HospitalNephrology Department, Heraklion University HospitalNephrology Department, Heraklion University HospitalNephrology Department, Heraklion University HospitalNephrology Department, Heraklion University HospitalFoundation for Research and Technology – HellasNephrology Department, Heraklion University HospitalDepartment of Nephrology, Saarland University Medical CenterNeurogenetics Laboratory Medical School, University of CreteNephrology Department, Heraklion University HospitalAbstract Background Dent disease is an X-linked disorder characterized by low molecular weight proteinuria (LMWP), hypercalciuria, nephrolithiasis and chronic kidney disease (CKD). It is caused by mutations in the chloride voltage-gated channel 5 (CLCN5) gene (Dent disease-1), or in the OCRL gene (Dent disease-2). It is associated with chronic metabolic acidosis; however metabolic alkalosis has rarely been reported. Case presentation We present a family with Dent-2 disease and a Bartter-like phenotype. The main clinical problems observed in the proband included a) primary phosphaturia leading to osteomalacia and stunted growth; b) elevated serum calcitriol levels, leading to hypercalcemia, hypercalciuria, nephrolithiasis and nephrocalcinosis; c) severe salt wasting causing hypotension, hyperaldosteronism, hypokalemia and metabolic alkalosis; d) partial nephrogenic diabetes insipidus attributed to hypercalcemia, hypokalemia and nephrocalcinosis; e) albuminuria, LMWP. Phosphorous repletion resulted in abrupt cessation of hypercalciuria and significant improvement of hypophosphatemia, physical stamina and bone histology. Years later, he presented progressive CKD with nephrotic range proteinuria attributed to focal segmental glomerulosclerosis (FSGS). Targeted genetic analysis for several phosphaturic diseases was unsuccessful. Whole Exome Sequencing (WES) revealed a c.1893C > A variant (Asp631Glu) in the OCRL gene which was co-segregated with the disease in male family members. Conclusions We present the clinical characteristics of the Asp631Glu mutation in the OCRL gene, presenting as Dent-2 disease with Bartter-like features. Phosphorous repletion resulted in significant improvement of all clinical features except for progressive CKD. Angiotensin blockade improved proteinuria and stabilized kidney function for several years. Graphical abstracthttps://doi.org/10.1186/s12882-022-02812-9Dent diseaseBartter syndromeOCRLCase report |
| spellingShingle | Eleni Drosataki Sevasti Maragkou Kleio Dermitzaki Ioanna Stavrakaki Dimitra Lygerou Helen Latsoudis Christos Pleros Ioannis Petrakis Ioannis Zaganas Kostas Stylianou Dent-2 disease with a Bartter-like phenotype caused by the Asp631Glu mutation in the OCRL gene BMC Nephrology Dent disease Bartter syndrome OCRL Case report |
| title | Dent-2 disease with a Bartter-like phenotype caused by the Asp631Glu mutation in the OCRL gene |
| title_full | Dent-2 disease with a Bartter-like phenotype caused by the Asp631Glu mutation in the OCRL gene |
| title_fullStr | Dent-2 disease with a Bartter-like phenotype caused by the Asp631Glu mutation in the OCRL gene |
| title_full_unstemmed | Dent-2 disease with a Bartter-like phenotype caused by the Asp631Glu mutation in the OCRL gene |
| title_short | Dent-2 disease with a Bartter-like phenotype caused by the Asp631Glu mutation in the OCRL gene |
| title_sort | dent 2 disease with a bartter like phenotype caused by the asp631glu mutation in the ocrl gene |
| topic | Dent disease Bartter syndrome OCRL Case report |
| url | https://doi.org/10.1186/s12882-022-02812-9 |
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