Dents disease is ultra rare genetic disease tranamitted as X-linked . Few hundreds of families reported in medical litureture.the female carries the disease and usually they have mild symptoms on other hands the male may progress to advanced CKD and ESRD .
Prevelance around 1 in 50000 males .approximately 30-80% of males with the disease will need renal replacement therapy usually at age 30 to 50 years ,representing overall small fraction <0.1 of patients on dialyaia in large international registries.
Its X-linked .there are two genetic mutation CLCN5 and OCRL1.The clinical presentation different between both genes.its classified as heridetery tubulointerstial disease.
Clinical Manifestations depends on genes affected the CLCN5 gen can cause Proximal tubule Dysfunction leading to loss of low-molecular-weight proteinuria this is the main hallmark of renal involvement.also can cause hypercalciuria which can cause Nephrocalcinosis ,nephrolithiasis and hematuria (microscopic or macroscopic).
As the disease progress with chronic tubular damage there will be fibrosis and scaring of the kidney which progress to advanced CKD and ESRD .
Other Manifestations including extrarenal mainly bone and skeltal due to phosphate loss and vitamin D metabolism abnormalities which will cause Rickets ,osteomalacia,deformities and short stature in children.
Diagnosis sometimes difficult and needs high clinical suspsion particularly young male with proteinuria, nephrocalcinosis, renal stone ,hypercalciuria with impaired renal function without clear cause on back ground of family history of renal disease .
Presence of low molecular proteinuria like β2-microglobulin, α1-microglobulin) is characteristics .picture of proximal tubular dysfunction in addition to aminoaciduria, phosphaturia, glycosuria,and hypercalciuria . CKD with hypophosphatemia and vitamin D abnormalities in rickets cases may help in diagnosis. kidney image may show Nephrocalcinosis and Kidney stones.
Genetic Testing cconsidred the Definitive Diagnosis to Identify mutation in CLCN5 (Dent-1, ~60% cases) or OCRL1 (Dent-2, ~15% cases).genetic test Confirms diagnosis and also helps with family counseling.
Treatment of dents disease usually conservative to slow the progression of CKD .this includes measures to treat the stone with adequte hydrartion , use of thized diuretic low salt intake , and use of pottasium citrate may help.
Other approach decrease proteinuria with RAASI inhibitors .also Measures directed to treat Bone Disease including Phosphate and Vitamin D analogs supplementation to correct bone metabolism abnormalities.Other measures including optimal BP control frequenint renal function monitoring and avoid nephrotoxic medication.
Once patient reach ESRD patient will need renal replacement therapy initiation. Tranplant is the best option of RRT. Of note the disease does not reoccur after kidney transplantation. As the donor kidney comes with normal tubular function.
