Dent's disease
Dent's disease (or Dent disease) is a rare X-linked recessive inherited condition that affects the proximal renal tubules of the kidney. It is one cause of Fanconi syndrome, and is characterized by tubular proteinuria, excess calcium in the urine, formation of calcium kidney stones, nephrocalcinosis, and chronic kidney failure. "Dent's disease" is often used to describe an entire group of familial disorders, including X-linked recessive nephrolithiasis with kidney failure, X-linked recessive hypophosphatemic rickets, and both Japanese and idiopathic low-molecular-weight proteinuria. About 60% of patients have mutations in the "CLCN5" gene  (Dent 1), which encodes a kidney-specific chloride/proton antiporter, and 15% of patients have mutations in the "OCRL1" gene (Dent 2). Signs and symptoms. Dent's disease often produces the following signs and symptoms: In a study of 25 patients with Dent's disease, 9 of 15 men, and one of 10 women suffered end-stage kidney disease by the age of 47. Genetics. Dent disease 1. Dent's disease is a X-linked recessive disorder. The males are prone to manifesting symptoms in early adulthood with symptoms of calculi, rickets or even with kidney failure in more severe  cases. In humans, gene "CLCN5" is located on chromosome Xp11.22, and has a 2238-bp coding sequence that consists of 11 exons that span 25 to 30 kb of genomic DNA and encode a 746-amino-acid protein. "CLCN5" belongs to the family of voltage-gated chloride channel genes ("CLCN1-CLCN7", "CLCKa" and "CLCKb") that have about 12 transmembrane domains. These chloride channels have an important role in the control of membrane excitability, transepithelial transport, and possibly cell volume. The mechanisms by which CLC-5 dysfunction results in hypercalciuria and the other features of Dent's disease remain to be elucidated . The identification of additional "CLCN5" mutations may help in these studies. Dent disease 2. Dent disease 2 (nephrolithiasis type 2) is associated with the "OCRL" gene. Both Lowe syndrome (oculocerebrorenal syndrome) and Dent disease can be caused by truncating or missense mutations in "OCRL". Diagnosis. Diagnosis is based on genetic study of CNCL5 gene. Treatment. As of today, no agreed-upon treatment of Dent's disease is known and no therapy has been formally accepted. Most treatment measures are supportive in nature: History. Dent's disease was first described by Charles Enrique Dent and M. Friedman in 1964, when they  reported two unrelated British boys with rickets associated with renal tubular damage characterized by hypercalciuria, hyperphosphaturia, proteinuria, and aminoaciduria. This set of symptoms was not given a name until 30 years later, when the nephrologist Oliver Wrong more fully described the disease. Wrong had studied with Dent and chose to name the disease after his mentor. Dent's disease is a genetic disorder caused by mutations in the gene "CLCN5", which encodes a kidney-specific voltage-gated chloride channel, a 746-amino-acid protein (CLC-5) with 12 to 13 transmembrane domains. It manifests itself through low-molecular-weight proteinuria, hypercalciuria , aminoaciduria and hypophosphataemia. Because of its rather rare occurrence, Dent's disease is often diagnosed as idiopathic hypercalciuria, i.e., excess calcium in urine with undetermined causes.