Dent disease is an X-linked recessive disorder of proximal tubule function, that is cause by mutations in one of the genes CLCN5 and OCRL1, Dent 1 and Dent 2 respectively. The disease is characterized clinically by low molecular weight proteinuria, nephrocalcinosis/nephrolithiasis, hypercalciuria, and progressive renal failure.
Dent disease is a rare disorder with only a few hundert cases published worldwide. However is can be surmised that many cases remain undetected because simply treated as recurrent nephrolithiasis.[Error: Macro 'ref' doesn't exist]
Low-molecular weight proteinuria is present in almost all patients with Dent disease. It is frequent in obligate female carriers even. Also female carriers may show a disposition to kidney stone formation. Based on these observations Hopes criteria were developed. The include (1) low-molecular-weight (LMW) proteinuria; (2) hypercalciuria; and (3) at least one of the following: nephrocalcinosis, kidney stones, renal insufficiency, hypophosphatemia, or hematuria.[Error: Macro 'ref' doesn't exist]
The symptom frequencies is male patients:
99% low-molecular-weight proteinuria (alpha1- and beta2-Microglobulin, Retinol binding protein)
95% hypercalciuria
75% nephrocalcinosis
50% nephrolithiasis
30-80% end-stage renal failure in the 3rd-5th decade
rickets (vitamin D metabolism)
night blindness (retinol binding)
hematuria (kidney stones)
Symptom frequencies in female patients:
In therapy, thiazide diuretics can be tried as they reduce hypercalciuria.
Proteinuria | |
Proteinuria is an early symptom. It is the most consistent symptom and detected in obligate female carriers even. Typically at the beginning, it is a low-molecular-weight (tubular) proteinuria (LMWP) that pattern may change however with disease progression. |
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Hypercalciuria | |
Hypercalciuria in Dent disease is a typical and early symptom but detected only if explicitly searched for. It accompanied by low molecular weight proteinuria and hypophosphatemia. As an x-linked recessive disorder boys are affected. |
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Hyperphosphaturia | |
Hyperphosphaturia is sometimes difficult to measure. However, it is of cardinal importance to the development of nephrocalcinosis and hypophaspatemia related bone disease. |
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Nephrocalcinosis | |
Nephrocalcinosis develops based on impaired renal calcium and phosphate handling. The probability to detect it increases with age. |
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Proximal tubular damage syndrome | |
Along with pathognomonical signs as hypercalciuria, LMW proteinuria, and nephrocalcinosis infrequently other signs of proximal tybular damage (Fanconi) can be found. |
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Urolithiasis | |
Along with nephrocalcinosis kidney stones may develop. In some patients, the frequent stone formation is the only clinically apparent symptom. |
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Osteomalacia | |
The cause of rickets in male patients with Dent disease are disturbances in calcium-, phophate balance, and vitamin D metabolism. |
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Renal insufficiency | |
Up to 80% of male patients reach end-stage renal failure in their 30-50th decade. Cause is progressive nephrocalcinosis and complications of recurrent nephrolithiasis. |
1. |
Hoopes RR et al. (2005) Dent Disease with mutations in OCRL1. |
2. |
Santo Y et al. (2004) Examination of megalin in renal tubular epithelium from patients with Dent disease. |
3. |
Ludwig M et al. (2004) Dent disease-like phenotype and the chloride channel ClC-4 (CLCN4) gene. |
4. |
None (2004) Megalin and proximal renal tubular dysfunction in Dent disease. |
5. |
Cobeñas CJ et al. (2004) A 3-year-old child with proteinuria and nephrocalcinosis. Suspicion of Dent disease. |
6. |
None (2006) [Dent disease (idiopathic tubular proteinuria): Pathogenesis, pathophysiology, and therapy] |
7. |
Ludwig M et al. (2006) Hypercalciuria in patients with CLCN5 mutations. |
8. |
Devuyst O et al. (2010) Dent's disease. |
9. |
OMIM.ORG article Omim 300009 |
10. |
Orphanet article Orphanet ID 1652 |
11. |
Wikipedia article Wikipedia EN (Dent's_disease) |