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). Dent's disease often produces the following signs and symptoms: Extreme thirst combined with dehydration, which leads to frequent urination Nephrolithiasis (kidney stones) Hypercalciuria (high urine calcium - >300 mg/d or >4 mg/kg per d with normal levels blood/serum calcium) Aminoaciduria (amino acids in urine) Phosphaturia (phosphate in urine) Glycosuria (glucose in urine) Kaliuresis (potassium in urine) Hyperuricosuria (excessive amounts of uric acid in the urine) Impaired urinary acidification Rickets In a study of 25 patients with Dent's disease, 9 of 15 men, and one of 10 women had end-stage kidney disease by the age of 47. 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.