Dents 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. "Dents 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
Dents 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
RicketsIn a study of 25 patients with Dents disease, 9 of 15 men, and one of 10 women had end-stage kidney disease by the age of 47. Genetics
Dent disease 1
Dents disease is a X-linked recessive disorder.
The impairment of Na transport in the distal convoluted tubule induces natriuresis and water loss, while increasing the reabsorption of calcium in this segment in a manner unrelated to sodium transport. Amiloride also increases distal tubular calcium reabsorption and has been used as a therapy for idiopathic hypercalciuria. A combination of 25 mg of chlorthalidone plus 5 mg of amiloride daily led to a substantial reduction in urine calcium in Dents patients, but urine pH was "significantly higher in patients with Dent’s disease than in those with idiopathic hypercalciuria (P < 0.03), and supersaturation for uric acid was consequently lower (P < 0.03)." For patients with osteomalacia, vitamin D or derivatives have been employed, apparently with success. Some lab tests on mice with CLC-5-related tubular damage showed a high-citrate diet preserved kidney function and delayed progress of kidney disease. History
Dents 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. Dents 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.